Mohammad Khan - Academia.edu (original) (raw)
Papers by Mohammad Khan
Prostaglandins, leukotrienes, and essential fatty acids, 2003
A role of indices of oxidative stress, oxidative injury, and abnormal membrane phospholipid, spec... more A role of indices of oxidative stress, oxidative injury, and abnormal membrane phospholipid, specifically the phospholipid essential polyunsaturated fatty acids (EPUFAs) metabolism has been suggested based on studies in separate groups of patients with or without medication. The current study investigated the relationship between these biochemical measures in first-episode psychotic patients (N=16) at baseline and after 6 months of antipsychotic treatment (N=5 each with risperidone and olanzapine) and compared them to matched normal subjects. The indices of oxidative stress included: antioxidant enzymes; superoxide dismutase, glutathione peroxidase and catalase; and the oxidative injury as the levels of plasma lipid peroxides. The key membrane EPUFA's been; linolenic acid, arachidonic acid, nervonic acid, docosapentaenoic acid and docosahexaenoic acid. Furthermore, the changes in these biochemical measures were correlated with clinical symptomatology. Data indicated that, at bas...
Journal of Ayub Medical College, Abbottabad : JAMC
Population-based data on the prevalence of diabetic retinopathy in Pakistan are lacking. We deter... more Population-based data on the prevalence of diabetic retinopathy in Pakistan are lacking. We determined the prevalence of diabetic retinopathy among individuals screened positive for diabetes in five community-based eye camps in northern Karachi, Pakistan. In summer 2002, five community-based eye camps were set up in Karachi, Pakistan's largest city. All individuals aged 30 years or older who visited the camps were requested to participate in the study. Those who agreed were screened for diabetes and those found to have the disease were referred to an eye hospital for diabetic retinopathy screening. Verbal informed consent was obtained from all participants at the examination site. Our main outcome measure was diabetic retinopathy, which was classified as non-proliferative diabetic retinopathy (NPDR), severe NPDR, and proliferative diabetic retinopathy (PDR). Our grading was based on clinical examination. A total of 912 subjects were screened for diabetes mellitus. Of these, 160 ...
Pattern of morphological variations was studied in seven cultivars of cotton viz. (1) DPL-41, (2)... more Pattern of morphological variations was studied in seven cultivars of cotton viz. (1) DPL-41, (2) DPL-20, (3) BAC-49, (4) DPL-50, (5) DPL-51, (6) JA/96-B and (7) DPL-90 by metroglyph and index score method (Anderson, 1957). Two most variable characters - plant height at maturity (PHM) and fibre yield per plant (FYP) were selected for X and Y axis, respectively. In
BMC Ophthalmology, 2006
Research exploring children&a... more Research exploring children's and their teachers' perceptions of eye health is lacking. This paper reports for the first time on perceptions of primary schoolchildren and their teachers of healthy and diseased eyes, things that keep eyes healthy and damage them, and what actions to be taken in case of an eye injury. Using draw and write technique, 160 boys and girls (9-12 years old) attending four primary schools in Abbottabad district, northern Pakistan, were invited to draw pictures in response to a set of semi-structured questions and then label them. Sixteen teachers who were currently teaching the selected students were interviewed one-on-one. Analysis of text accompanying 800 drawings and of the interview scripts revealed that most children and teachers perceived healthy eyes to be those which could see well, and diseased eyes to be those which have redness, watering, dirty discharge, pain, and itching; or those which have "weak eyesight" and blindness. Among things that students and teachers thought damage the eyes included sun, television, and sharp pointed objects, particularly pencils. Teachers noted that children with eye problems "have difficulty seeing the blackboard…
The Surgeon, 2009
Although there is much consensus, certain controversies still exist regarding the pathology of Fo... more Although there is much consensus, certain controversies still exist regarding the pathology of Fournier's gangrene. The purpose of this study was to determine the prevalence of the disease in the catchment area of the three teaching hospitals, to identify the systemic predisposing factors and local aetiological factors, and to assess the recommended role of aggressive surgical debridement as a part of treatment. This prospective study was conducted in the surgical departments of three tertiary care hospitals of the Khyber Medical University, Peshawar, Pakistan, from 1 January 2002 to 30 June 2007. Detailed history and examination of all patients were carried out to reach the diagnosis of Fournier's gangrene. After initial resuscitation, patients were treated aggressively, including surgical debridement. Sixty patients were studied in the study period. The male to female ratio was 5:1. The age range was 20-75 years with mean 47+17.4 (SD) years. The socioeconomic status of patients was poor (the average income was less than 50perweek)in36(6050 per week) in 36 (60%) and 24 (40%) were middle class (the average income being 50perweek)in36(6050-100 per week). Thirty-nine patients (65%) presented in the hot humid months of the year. Extent of the disease was scrotum in 18 patients (30%), perineum in 30 (50%) and abdominal wall in 12 (20%). Systemic predisposing factors identified in our study were diabetes mellitus in 20 (33.33%) patients, chronic alcohol abuse in two (3.33%) and long-standing steroid therapy in four (6.67%) while in 34 patients (56.67%) no cause was identified. The local aetiological origin of Fournier's gangrene was urogenital in 14 (23.33%) patients, anorectal in 10 (16.67%) and cutaneous in 8 (13.33%) and no local pathologies could be identified in 28 (46.67%) patients. The mean time interval between first symptom and initial treatment was 2.5 days with a range of 1-7 days. Number of debridement sessions per patient was 2-6 (mean, 3.15). Mean hospital stay was 31+7 (SD) with a range of 10-50 days. Morbidity was 80%. Four patients (6.67%) died. Three of these patients presented to hospital 5-6 days too late. Fournier's gangrene is not an uncommon disease in South Asia. Systemic predisposition such as diabetes mellitus, long-standing steroid therapy, chronic alcoholism and even the hot humid season can contribute to this dreadful disease. Local causes in the form of urogenital, anorectal and cutaneous disorders may trigger this disease in some patients. Early recognition of disease and aggressive surgical debridement are the main treatments.
Steroids, 2007
Estrogen is an important hormone signal that regulates multiple tissues and functions in the body... more Estrogen is an important hormone signal that regulates multiple tissues and functions in the body. This review focuses on the neurotrophic and neuroprotective actions of estrogen in the brain, with particular emphasis on estrogen actions in the hippocampus, cerebral cortex and striatum. Sex differences in the risk, onset and severity of neurodegenerative disease such as Alzheimer's disease, Parkinson's disease and stroke are well known, and the potential role of estrogen as a neuroprotective factor is discussed in this context. The review assimilates a complex literature that spans research in humans, non-human primates and rodent animal models and attempts to contrast and compare the findings across species where possible. Current controversies regarding the WHI (Women's Health Initiative) study, its ramifications, concerns and the new studies needed to address these concerns are also addressed. Signaling mechanisms underlying estrogen-induced neuroprotection and synaptic plasticity are reviewed, including the important concepts of genomic versus nongenomic mechanisms, types of estrogen receptor involved and their subcellular targeting, and implicated downstream signaling pathways and mediators. Finally, a multicellular mode of estrogen action in the regulation of neuronal survival and neurotrophism is discussed, as are potential future directions for the field.
Schizophrenia Research, 2002
Abnormal membrane phospholipid essential polyunsaturated fatty acid (EPUFA) metabolism (i.e., red... more Abnormal membrane phospholipid essential polyunsaturated fatty acid (EPUFA) metabolism (i.e., reduced incorporation into phospholipids and increased breakdown) has been suggested to contribute to the etiopathophysiology of schizophrenia. However, most of the published studies have reported changes in the levels of membrane EPUFA in chronic medicated patients or in drug-naive patients long after onset of illness (1-2 years). Since the EPUFA metabolism can be altered by years of untreated illness or differentially altered by various antipsychotics, the significance of EPUFA membrane status to schizophrenia psychopathophysiology is unclear. We report the erythrocyte membrane EPUFA levels in drug-naive patients within +/- 4.5 days of onset of psychosis from an Army Medical Center, and in patients treated years with antipsychotics from a Veterans Affairs Medical Center. The levels of plasma lipid peroxides (TBARS, thiobarbituric acid reactive substances), products of damaged EPUFAs, were also determined. The levels of EPUFAs, particularly arachidonic acid (AA) and docosahexaenoic acid (DHA) were significantly lower (P < 0.001) in drug-naive patients at the onset of psychosis compared to matched normal controls. These lower EPUFA levels were associated with significantly higher levels of TBARS in patients (P < 0.001). The levels of AA and DHA were also lower (P < 0.001) and TBARS higher in chronic medicated patients than normal controls. However, the EPUFA levels were higher in chronic medicated patients than drug-naive first-episode patients. These data indicate that lower membrane AA and DHA most likely predate the illness and probably contribute to the onset of illness, and furthermore treatment with some antipsychotics may increase the levels of EPUFAs. The lipid peroxidation data suggest that possible increased oxidative stress, either as a part of the illness and/or its treatment with antipsychotics, may be one of the mechanisms of reduced membrane EPUFAs. These findings may have a significant impact on improving strategies for supplementation of EPUFAs and antioxidants to improve the outcome of schizophrenia.
Schizophrenia Research, 2002
Recently, apolipoprotein D (apoD), a protein that is involved in the essential polyunsaturated fa... more Recently, apolipoprotein D (apoD), a protein that is involved in the essential polyunsaturated fatty acid (EPUFA) transport and metabolism, and neuronal growth and regeneration was reported to have increased in the postmortem brain and decreased in the serum of schizophrenia patients. We studied the plasma apoD levels in never-medicated schizophrenic patients at the onset of psychosis and in chronic patients with clozapine treatment. Plasma apoD levels were elevated in never-medicated patients at the first-episode of psychosis compared to normals (P = 0.047). Interestingly, the increase in apoD level was even more significant in chronic patients treated with clozapine compared to normals and first-episode patients (P = 0.008 and P = 0.03, respectively). The increased apoD level in never-medicated first-episode patients indicate that this increase probably predates the illness, since the duration of illness was < 5 days. Similarly, an even larger increase in apoD after clozapine treatment may be associated with its prophylactic effects, since the psychopathological scores were significantly reduced and the clozapine treatment has been found to increase the EPUFA membrane levels. These altered levels of apoD may help to understand the nature and possible mechanism of phospholipid membrane pathology in schizophrenia.
Schizophrenia Research, 2003
Nerve growth factor (NGF) has been found to play a crucial role in the neuroplasticity of predomi... more Nerve growth factor (NGF) has been found to play a crucial role in the neuroplasticity of predominantly cholinergic neurons in brain development, and neuronal survival following brain injury, which reflect in cognitive performance. Wide ranges of neurodevelopmental abnormalities have been reported in schizophrenic patients, who also show poor cognitive performance. We report plasma NGF levels in never-medicated first-episode psychotic (FEP; N = 24) and chronic medicated schizophrenic patients (N = 24). NGF levels were determined in plasma by Enzyme-Linked ImmunoSorbent Assay (ELISA). Plasma NGF levels were significantly lower in both FEP and medicated chronic patients as compared to normal subjects ( P < 0.001). However, NGF levels were significantly higher in chronic schizophrenic patients, which were treated with antipsychotics as compared to FEP ( P < 0.05). Moreover, NGF levels in chronic patients treated with atypical antipsychotics were markedly higher as compared to patients treated with typical antipsychotics ( P < 0.05). Lower NGF levels in FEP patients at the onset of psychosis may have implications for the neurodevelopmental abnormalities. However, higher NGF levels in chronic patients treated with atypical antipsychotics may have implications for the treatment outcome. D
Psychopharmacology, 2004
Rationale: Recently, we reported that compared to haloperidol, chronic exposure to either the ris... more Rationale: Recently, we reported that compared to haloperidol, chronic exposure to either the risperidone (RISP) or olanzapine (OLZ) resulted in superior effects on spatial learning performance as well as the cholinergic neurons, although the mechanism for these effects was not addressed. Objectives: The objective of this study was to investigate one plausible mechanism whereby RISP and OLZ exert superior effects on cholinergic neurons, i.e. positive effects on nerve growth factor (NGF), which is known to regulate the brain cholinergic activity as well as cognitive function. Therefore, the effects of chronic exposure to HAL, RISP, or OLZ on the expression of NGF and choline acetyltransferase (ChAT) in the hippocampus (i.e. a brain area well known to be involved in cognitive function and known to receive major cholinergic projections from the medial septum) were compared. Methods: Rats were treated with HAL (1 or 2 mg/kg per day), RISP (1.25 or 2.5 mg/kg per day), or OLZ (5 or 10 mg/kg per day) for 45 days in drinking water. NGF and ChAT were measured by immunohistochemistry and NGF protein was also measured by an enzyme-linked ImmunoSorbent assay. Results: Compared to controls, HAL exposure resulted in a marked reduction in NGF immunoreactivity in the hippocampal dentate gyrus (DG), CA1 and CA3 areas. In contrast, RISP did not alter, while OLZ significantly increased levels of NGF. These changes in NGF levels corresponded well with changes in ChAT immunoreactivity in the hippocampus and the medial septum. Conclusions: These preclinical data, combined with previously published behavioral results, support the premise that OLZ and RISP, in contrast to HAL, preserve cholinergic pathways and cognitive function via superior effects on NGF expression and are thus therapeutically superior for extended use.
PLANT PHYSIOLOGY, 2010
ROXY1 and ROXY2 are CC-type floral glutaredoxins with redundant functions in Arabidopsis (Arabido... more ROXY1 and ROXY2 are CC-type floral glutaredoxins with redundant functions in Arabidopsis (Arabidopsis thaliana) anther development. We show here that plants lacking the basic leucine-zipper transcription factors TGA9 and TGA10 have defects in male gametogenesis that are strikingly similar to those in roxy1 roxy2 mutants. In tga9 tga10 mutants, adaxial and abaxial anther lobe development is differentially affected, with early steps in anther development blocked in adaxial lobes and later steps affected in abaxial lobes. Distinct from roxy1 roxy2, microspore development in abaxial anther lobes proceeds to a later stage with the production of inviable pollen grains contained within nondehiscent anthers. Histological analysis shows multiple defects in the anther dehiscence program, including abnormal stability and lignification of the middle layer and defects in septum and stomium function. Compatible with these defects, TGA9 and TGA10 are expressed throughout early anther primordia but resolve to the middle and tapetum layers during meiosis of pollen mother cells. Several lines of evidence suggest that ROXY promotion of anther development is mediated in part by TGA9 and TGA10. First, TGA9 and TGA10 expression overlaps with ROXY1/2 during anther development. Second, TGA9/10 and ROXY1/2 operate downstream of SPOROCYTELESS/NOZZLE, where they positively regulate a common set of genes that contribute to tapetal development. Third, TGA9 and TGA10 directly interact with ROXY proteins in yeast and in plant cell nuclei. These findings suggest that activation of TGA9/10 transcription factors by ROXY-mediated modification of cysteine residues promotes anther development, thus broadening our understanding of how redox-regulated TGA factors function in plants.
Ophthalmic Epidemiology, 2006
To assess the annual number of glaucoma operations and admissions in the public sector tertiary c... more To assess the annual number of glaucoma operations and admissions in the public sector tertiary care hospitals in Pakistan. Eye departments in all 18 public tertiary care centers in the country were requested to provide data on the number of glaucoma operations and admissions during 1998. Of these, 13 hospitals agreed to participate. Eye departments&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; log books or patients&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; records were used to collect data retrospectively on the total number of eye admissions, the total number of glaucoma admissions, the type of glaucoma, and the total number and type of glaucoma operations. Glaucoma accounted for 8.1% (1,942/23,931) of all eye admissions. Open-angle glaucoma was responsible for 37.6% or 731 glaucoma admissions followed by secondary glaucoma (35.0%) and angle-closure glaucoma (18.2%). During 1998, 1,407 glaucoma-related operations were performed in the selected hospitals. The mean (+/-SD) and the median number of operations performed were 108.2 (+/-59.6) and 112 (range: 17-206), respectively. Trabeculectomies accounted for 1,043 (74.1 %) of all procedures. Their number ranged from 16 to 170 (median: 84) in the selected hospitals. We believe that the annual number of glaucoma operations performed in the public tertiary care hospitals in Pakistan is far less than required. In-depth research is therefore needed to explain if this is because of gaps in service provision or a genuine shift to medical management of glaucoma on an outpatient basis.
Ophthalmic Epidemiology, 2008
Purpose: To assess visual functioning and quality of life in a representative sample of normally ... more Purpose: To assess visual functioning and quality of life in a representative sample of normally sighted, visually impaired and cataract operated individuals aged ≥30 years in Pakistan. Methods: As part of the Pakistan National Blindness and Visual Impairment Survey, visual functioning (VF) and quality of life (QOL) questionnaires were administered to participants with presenting visual acuity less than 6/60 in either eye, aphakes/pseudophakes and a phakic sample with normal acuity (≥6/12 both eyes). Results: Of 16,507 adults included in the survey, 2329 questionnaires were administered. There were strong correlations between visual acuity and VF/QOL. Mean VF and median QOL scores in normally sighted phakic individuals were 81.1 and 88.9, respectively, but were only 34.8 and 64.9 in blind unoperated individuals. In the cataract operated population overall mean VF and median QOL scores were 49.3 and 75.0. Both VF and QOL scores were lower in operated individuals than unoperated individuals (p < 0.001). Among operated individuals, rural dwelling and illiteracy were associated with lower VF and QOL scores (p all < 0.02). Although in multivariable analysis bilateral pseudophakes had similar VF scores to bilateral aphakes they had significantly better QOL scores (p = 0.001). Conclusions: Cataract surgery in Pakistan has not led to VF and QOL scores equivalent to those in unoperated individuals with the same levels of visual acuity. The higher proportion of intraocular lens surgery in recent years is likely to improve QOL following cataract surgery. Further focus is needed on rural and illiterate populations, to ensure that they achieve comparable VF/QOL outcomes following surgery.
Ophthalmic Epidemiology, 2009
To identify children aged 0-72 months with blinding xerophthalmia in the North West Frontier Prov... more To identify children aged 0-72 months with blinding xerophthalmia in the North West Frontier Province (NWFP) and its adjoining Federally Administered Tribal Areas (FATA) in Pakistan, using a new surveillance system, and to describe socio-economic and other characteristics of reported cases. All ophthalmologists in district headquarter hospitals in NWFP and agency headquarter hospitals in FATA were requested to participate in a surveillance programme for the detection of blinding xerophthalmia (corneal xerosis, corneal ulcers, keratomalacia and corneal scars related to vitamin A deficiency) for children aged 0-72 months. The surveillance included reporting of each case of blinding xerophthalmia presenting to the participating eye units over a period of 12 months and recording their socio-economic and other related characteristics. Seventy six cases of blinding xerophthalmia were reported and there was almost no gender difference. Children came from 19 of 31 districts and agencies in NWFP and FATA with a working ophthalmologist. The commonest age at presentation was 25-48 months and almost half of them belonged to households with a monthly income of &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; Pak Rs. 1200 (US $ &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 20). Precipitating systemic illnesses were diarrhea and fever with cough in 63.2% and 56.6% cases, respectively. Almost a third of children aged &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 9 months had not been immunized against measles. A quarter of all children had not been adequately breast-fed, and 7 children (9%) had never been breastfed. Majority of the cases presented during summer and autumn months. Our surveillance data provide evidence that blinding xerophthalmia does occur in children in NWFP and its adjoining FATA. The surveillance system identified high risk age groups, systemic illnesses, seasons and community groups. The detection system detects minimal numbers of cases and it is likely that the problem is even more severe.
Neuroscience Letters, 2004
Recently, we have reported studies in rats showing that the atypical antipsychotic olanzapine (OL... more Recently, we have reported studies in rats showing that the atypical antipsychotic olanzapine (OLZ), in contrast to haloperidol (HAL), was not associated with reduction of markers of central cholinergic neurons as well as decrements in cognitive performance after chronic exposure. We compared the effect of 45 day chronic exposure of HAL (2 mg/kg per day) to OLZ (10 mg/kg per day) on brain-derived neurotrophic factor (BDNF)) and its high affinity receptor TrkB in rat hippocampus. Since the use of OLZ is presently preferred over HAL in patients, effects of its post-treatment on HAL-induced changes in the expression of BDNF and its TrkB receptor were also investigated. OLZ was administered after 45 days of HAL exposure. HAL, but not OLZ, significantly reduced the levels of BDNF in hippocampus. These changes in BDNF paralleled the levels of TrkB receptors. Furthermore, post-treatment with OLZ markedly restored the HAL treatment associated reductions in both BDNF and TrkB receptors in hippocampus. q
Journal of Surgical Research, 2009
Journal of Psychiatric Research, 2004
Previously we reported that chronic exposure to haloperidol (HAL), but not the atypical antipsych... more Previously we reported that chronic exposure to haloperidol (HAL), but not the atypical antipsychotics risperidone (RISP) or clozapine (CLOZ), resulted in reductions in brain choline acetyltransferase (ChAT) immunoreactivity and impaired water maze task performance in rats. In the present study, we compared the effects of these antipsychotic drugs on the expression of nerve growth factor (NGF) as well ChAT the in the rat cortex and nucleus basalis of Meynert (NBM) in an effort to determine the underlying mechanism for the differential drug effects observed previously. We also evaluated the effects of these compounds in a crossover design to evaluate specific neurochemical consequences of switching between typical and atypical antipsychotics, a common practice observed in the clinical setting. Male Wistar rats (250-300 g) were exposed to HAL (2.0 mg/kg/day), RISP (2.5 mg/kg/day), or CLOZ (20 mg/kg/day) for 45 days or a pre-treatment regimen consisting of administering either RISP/HAL (i.e., RISP followed by HAL) or CLOZ/HAL, or a post-treatment regimen consisting of administering: HAL/RISP or HAL/CLOZ. The duration of each treatment in the crossover study was also 45 days. NGF and ChAT immunoreactivity were measured by quantitative immunohistochemistry in some sub-cerebral cortical regions and NBM after drug exposures. NGF protein was also measured by an enzymelinked ImmunoSorbent assay (ELISA) in rat sensorimotor cortex. The results indicated that HAL (but not RISP or CLOZ) significantly reduced NGF levels in some sub-cortical regions and ChAT immunoreactivity in both cortex and NBM. However, pretreatment with CLOZ prevented the HAL-associated decreases in NGF and ChAT, while post-treatment with either RISP or CLOZ (i.e., after the administration of HAL) appeared to restore NGF and ChAT to control levels. These data indicate that antipsychotic drugs exert dissimilar effects on the levels of NGF and ChAT in the brain, which may contribute to their differential effects on cognitive function. The crossover data further suggest that certain atypical antipsychotic drugs (e.g., clozapine) may have the potential to prevent or reverse the deleterious effects of HAL on important neurochemical substrates of cognitive function.
Journal of Neuroscience Research, 2007
Basic fibroblast growth factor (bFGF) and transforming growth factor-b1 (TGF-b1) play an importan... more Basic fibroblast growth factor (bFGF) and transforming growth factor-b1 (TGF-b1) play an important role in proliferation, differentiation, and survival of malignant gliomas and in normal glial cell biology. Because of these critical roles, potential interactions between these key growth factors were investigated. We previously demonstrated that bFGF potently stimulates TGF-b1 release from rat glioma cells. The purpose of the present study was to elucidate the mechanism(s) of this regulatory effect, establish its functional importance, and examine whether it extends to nontransformed rat hypothalamic astrocytes (RHA). The results revealed that RHA express the high-affinity FGF(1-4) receptors, and similarly to glioma cells, bFGF stimulated TGF-b1 release in an isoform-specific manner. A mediatory role for ERK signaling in bFGF-induced TGF-b release was suggested by the fact that MEK1 inhibition prevented this effect. Additionally, bFGF enhanced MEK1/2 phosphorylation and ERK activation/nuclear translocation, which culminated in increased activity of AP-1-mediated gene transcription. bFGF markedly induced TGF-b1 mRNA levels in an isoform-specific manner, an effect that was dependent on MEK/ERK/AP-1 signaling. Functionally, bFGF-induced proliferation of glioma cells was attenuated by MEK/ERK inhibition or immunoneutralization of TGF-b1, suggesting that this pathway may have important implications for brain tumor progression. V V C 2007 Wiley-Liss, Inc.
Journal of Antimicrobial Chemotherapy, 2010
To compare and contrast the geographic and demographic distribution of bro beta-lactamase and ant... more To compare and contrast the geographic and demographic distribution of bro beta-lactamase and antibiotic MIC(50/90) for 1440 global Moraxella catarrhalis isolates obtained from children and adults between 2001 and 2002. One thousand four hundred and forty M. catarrhalis isolates originating from seven world regions were investigated. The isolates were recovered from 411 children &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;5 years of age and 1029 adults &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;20 years of age. PCR-restriction fragment length polymorphism (RFLP) was performed to determine bro prevalence and to distinguish between bro types. MIC values of 12 different antibiotics were determined using the CLSI (formerly NCCLS) broth microdilution method. Of the 1440 isolates, 1313 (91%) possessed the bro-1 gene and 64 (4%) possessed the bro-2 gene. Additionally, the prevalence of bro positivity between the child and adult age groups was significantly different (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001), though bro-1 and bro-2 prevalences within age groups were not significantly different. Consistently higher beta-lactam MICs were observed for M. catarrhalis isolates originating in the Far East. Significant correlations in MICs were observed for several antibiotic combinations, including all five beta-lactams with each other, and among the two quinolones. The worldwide prevalence of bro gene carriage in clinical isolates of M. catarrhalis is now approaching 95%, with children significantly more likely to harbour bro-positive isolates than adults. Further, statistically significant differences in the distribution of beta-lactam MICs were observed between different world regions, particularly with respect to the Far East.
Infection and Immunity, 2002
The attenuation and immunogenicity of two novel Salmonella vaccine strains, Salmonella enterica s... more The attenuation and immunogenicity of two novel Salmonella vaccine strains, Salmonella enterica serovar Typhi (Ty2 ⌬aroC ⌬ssaV, designated ZH9) and S. enterica serovar Typhimurium (TML ⌬aroC ⌬ssaV, designated WT05), were evaluated after their oral administration to volunteers as single escalating doses of 10 7 , 10 8 , or 10 9 CFU. ZH9 was well tolerated, not detected in blood, nor persistently excreted in stool. Six of nine volunteers elicited anti-serovar Typhi lipopolysaccharide (LPS) immunoglobulin A (IgA) antibody-secreting cell (ASC) responses, with three of three vaccinees receiving 10 8 and two of three receiving 10 9 CFU which elicited high-titer LPS-specific serum IgG. WT05 was also well tolerated with no diarrhea, although the administration of 10 8 and 10 9 CFU resulted in shedding in stools for up to 23 days. Only volunteers immunized with 10 9 CFU of WT05 mounted detectable serovar Typhimurium LPS-specific ASC responses and serum antibody responses were variable. These data indicate that mutations in type III secretion systems may provide a route to the development of live vaccines in humans and highlight significant differences in the potential use of serovars Typhimurium and Typhi.
Prostaglandins, leukotrienes, and essential fatty acids, 2003
A role of indices of oxidative stress, oxidative injury, and abnormal membrane phospholipid, spec... more A role of indices of oxidative stress, oxidative injury, and abnormal membrane phospholipid, specifically the phospholipid essential polyunsaturated fatty acids (EPUFAs) metabolism has been suggested based on studies in separate groups of patients with or without medication. The current study investigated the relationship between these biochemical measures in first-episode psychotic patients (N=16) at baseline and after 6 months of antipsychotic treatment (N=5 each with risperidone and olanzapine) and compared them to matched normal subjects. The indices of oxidative stress included: antioxidant enzymes; superoxide dismutase, glutathione peroxidase and catalase; and the oxidative injury as the levels of plasma lipid peroxides. The key membrane EPUFA's been; linolenic acid, arachidonic acid, nervonic acid, docosapentaenoic acid and docosahexaenoic acid. Furthermore, the changes in these biochemical measures were correlated with clinical symptomatology. Data indicated that, at bas...
Journal of Ayub Medical College, Abbottabad : JAMC
Population-based data on the prevalence of diabetic retinopathy in Pakistan are lacking. We deter... more Population-based data on the prevalence of diabetic retinopathy in Pakistan are lacking. We determined the prevalence of diabetic retinopathy among individuals screened positive for diabetes in five community-based eye camps in northern Karachi, Pakistan. In summer 2002, five community-based eye camps were set up in Karachi, Pakistan's largest city. All individuals aged 30 years or older who visited the camps were requested to participate in the study. Those who agreed were screened for diabetes and those found to have the disease were referred to an eye hospital for diabetic retinopathy screening. Verbal informed consent was obtained from all participants at the examination site. Our main outcome measure was diabetic retinopathy, which was classified as non-proliferative diabetic retinopathy (NPDR), severe NPDR, and proliferative diabetic retinopathy (PDR). Our grading was based on clinical examination. A total of 912 subjects were screened for diabetes mellitus. Of these, 160 ...
Pattern of morphological variations was studied in seven cultivars of cotton viz. (1) DPL-41, (2)... more Pattern of morphological variations was studied in seven cultivars of cotton viz. (1) DPL-41, (2) DPL-20, (3) BAC-49, (4) DPL-50, (5) DPL-51, (6) JA/96-B and (7) DPL-90 by metroglyph and index score method (Anderson, 1957). Two most variable characters - plant height at maturity (PHM) and fibre yield per plant (FYP) were selected for X and Y axis, respectively. In
BMC Ophthalmology, 2006
Research exploring children&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;a... more Research exploring children&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s and their teachers&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; perceptions of eye health is lacking. This paper reports for the first time on perceptions of primary schoolchildren and their teachers of healthy and diseased eyes, things that keep eyes healthy and damage them, and what actions to be taken in case of an eye injury. Using draw and write technique, 160 boys and girls (9-12 years old) attending four primary schools in Abbottabad district, northern Pakistan, were invited to draw pictures in response to a set of semi-structured questions and then label them. Sixteen teachers who were currently teaching the selected students were interviewed one-on-one. Analysis of text accompanying 800 drawings and of the interview scripts revealed that most children and teachers perceived healthy eyes to be those which could see well, and diseased eyes to be those which have redness, watering, dirty discharge, pain, and itching; or those which have &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;weak eyesight&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; and blindness. Among things that students and teachers thought damage the eyes included sun, television, and sharp pointed objects, particularly pencils. Teachers noted that children with eye problems &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;have difficulty seeing the blackboard…
The Surgeon, 2009
Although there is much consensus, certain controversies still exist regarding the pathology of Fo... more Although there is much consensus, certain controversies still exist regarding the pathology of Fournier's gangrene. The purpose of this study was to determine the prevalence of the disease in the catchment area of the three teaching hospitals, to identify the systemic predisposing factors and local aetiological factors, and to assess the recommended role of aggressive surgical debridement as a part of treatment. This prospective study was conducted in the surgical departments of three tertiary care hospitals of the Khyber Medical University, Peshawar, Pakistan, from 1 January 2002 to 30 June 2007. Detailed history and examination of all patients were carried out to reach the diagnosis of Fournier's gangrene. After initial resuscitation, patients were treated aggressively, including surgical debridement. Sixty patients were studied in the study period. The male to female ratio was 5:1. The age range was 20-75 years with mean 47+17.4 (SD) years. The socioeconomic status of patients was poor (the average income was less than 50perweek)in36(6050 per week) in 36 (60%) and 24 (40%) were middle class (the average income being 50perweek)in36(6050-100 per week). Thirty-nine patients (65%) presented in the hot humid months of the year. Extent of the disease was scrotum in 18 patients (30%), perineum in 30 (50%) and abdominal wall in 12 (20%). Systemic predisposing factors identified in our study were diabetes mellitus in 20 (33.33%) patients, chronic alcohol abuse in two (3.33%) and long-standing steroid therapy in four (6.67%) while in 34 patients (56.67%) no cause was identified. The local aetiological origin of Fournier's gangrene was urogenital in 14 (23.33%) patients, anorectal in 10 (16.67%) and cutaneous in 8 (13.33%) and no local pathologies could be identified in 28 (46.67%) patients. The mean time interval between first symptom and initial treatment was 2.5 days with a range of 1-7 days. Number of debridement sessions per patient was 2-6 (mean, 3.15). Mean hospital stay was 31+7 (SD) with a range of 10-50 days. Morbidity was 80%. Four patients (6.67%) died. Three of these patients presented to hospital 5-6 days too late. Fournier's gangrene is not an uncommon disease in South Asia. Systemic predisposition such as diabetes mellitus, long-standing steroid therapy, chronic alcoholism and even the hot humid season can contribute to this dreadful disease. Local causes in the form of urogenital, anorectal and cutaneous disorders may trigger this disease in some patients. Early recognition of disease and aggressive surgical debridement are the main treatments.
Steroids, 2007
Estrogen is an important hormone signal that regulates multiple tissues and functions in the body... more Estrogen is an important hormone signal that regulates multiple tissues and functions in the body. This review focuses on the neurotrophic and neuroprotective actions of estrogen in the brain, with particular emphasis on estrogen actions in the hippocampus, cerebral cortex and striatum. Sex differences in the risk, onset and severity of neurodegenerative disease such as Alzheimer's disease, Parkinson's disease and stroke are well known, and the potential role of estrogen as a neuroprotective factor is discussed in this context. The review assimilates a complex literature that spans research in humans, non-human primates and rodent animal models and attempts to contrast and compare the findings across species where possible. Current controversies regarding the WHI (Women's Health Initiative) study, its ramifications, concerns and the new studies needed to address these concerns are also addressed. Signaling mechanisms underlying estrogen-induced neuroprotection and synaptic plasticity are reviewed, including the important concepts of genomic versus nongenomic mechanisms, types of estrogen receptor involved and their subcellular targeting, and implicated downstream signaling pathways and mediators. Finally, a multicellular mode of estrogen action in the regulation of neuronal survival and neurotrophism is discussed, as are potential future directions for the field.
Schizophrenia Research, 2002
Abnormal membrane phospholipid essential polyunsaturated fatty acid (EPUFA) metabolism (i.e., red... more Abnormal membrane phospholipid essential polyunsaturated fatty acid (EPUFA) metabolism (i.e., reduced incorporation into phospholipids and increased breakdown) has been suggested to contribute to the etiopathophysiology of schizophrenia. However, most of the published studies have reported changes in the levels of membrane EPUFA in chronic medicated patients or in drug-naive patients long after onset of illness (1-2 years). Since the EPUFA metabolism can be altered by years of untreated illness or differentially altered by various antipsychotics, the significance of EPUFA membrane status to schizophrenia psychopathophysiology is unclear. We report the erythrocyte membrane EPUFA levels in drug-naive patients within +/- 4.5 days of onset of psychosis from an Army Medical Center, and in patients treated years with antipsychotics from a Veterans Affairs Medical Center. The levels of plasma lipid peroxides (TBARS, thiobarbituric acid reactive substances), products of damaged EPUFAs, were also determined. The levels of EPUFAs, particularly arachidonic acid (AA) and docosahexaenoic acid (DHA) were significantly lower (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001) in drug-naive patients at the onset of psychosis compared to matched normal controls. These lower EPUFA levels were associated with significantly higher levels of TBARS in patients (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). The levels of AA and DHA were also lower (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001) and TBARS higher in chronic medicated patients than normal controls. However, the EPUFA levels were higher in chronic medicated patients than drug-naive first-episode patients. These data indicate that lower membrane AA and DHA most likely predate the illness and probably contribute to the onset of illness, and furthermore treatment with some antipsychotics may increase the levels of EPUFAs. The lipid peroxidation data suggest that possible increased oxidative stress, either as a part of the illness and/or its treatment with antipsychotics, may be one of the mechanisms of reduced membrane EPUFAs. These findings may have a significant impact on improving strategies for supplementation of EPUFAs and antioxidants to improve the outcome of schizophrenia.
Schizophrenia Research, 2002
Recently, apolipoprotein D (apoD), a protein that is involved in the essential polyunsaturated fa... more Recently, apolipoprotein D (apoD), a protein that is involved in the essential polyunsaturated fatty acid (EPUFA) transport and metabolism, and neuronal growth and regeneration was reported to have increased in the postmortem brain and decreased in the serum of schizophrenia patients. We studied the plasma apoD levels in never-medicated schizophrenic patients at the onset of psychosis and in chronic patients with clozapine treatment. Plasma apoD levels were elevated in never-medicated patients at the first-episode of psychosis compared to normals (P = 0.047). Interestingly, the increase in apoD level was even more significant in chronic patients treated with clozapine compared to normals and first-episode patients (P = 0.008 and P = 0.03, respectively). The increased apoD level in never-medicated first-episode patients indicate that this increase probably predates the illness, since the duration of illness was &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 5 days. Similarly, an even larger increase in apoD after clozapine treatment may be associated with its prophylactic effects, since the psychopathological scores were significantly reduced and the clozapine treatment has been found to increase the EPUFA membrane levels. These altered levels of apoD may help to understand the nature and possible mechanism of phospholipid membrane pathology in schizophrenia.
Schizophrenia Research, 2003
Nerve growth factor (NGF) has been found to play a crucial role in the neuroplasticity of predomi... more Nerve growth factor (NGF) has been found to play a crucial role in the neuroplasticity of predominantly cholinergic neurons in brain development, and neuronal survival following brain injury, which reflect in cognitive performance. Wide ranges of neurodevelopmental abnormalities have been reported in schizophrenic patients, who also show poor cognitive performance. We report plasma NGF levels in never-medicated first-episode psychotic (FEP; N = 24) and chronic medicated schizophrenic patients (N = 24). NGF levels were determined in plasma by Enzyme-Linked ImmunoSorbent Assay (ELISA). Plasma NGF levels were significantly lower in both FEP and medicated chronic patients as compared to normal subjects ( P < 0.001). However, NGF levels were significantly higher in chronic schizophrenic patients, which were treated with antipsychotics as compared to FEP ( P < 0.05). Moreover, NGF levels in chronic patients treated with atypical antipsychotics were markedly higher as compared to patients treated with typical antipsychotics ( P < 0.05). Lower NGF levels in FEP patients at the onset of psychosis may have implications for the neurodevelopmental abnormalities. However, higher NGF levels in chronic patients treated with atypical antipsychotics may have implications for the treatment outcome. D
Psychopharmacology, 2004
Rationale: Recently, we reported that compared to haloperidol, chronic exposure to either the ris... more Rationale: Recently, we reported that compared to haloperidol, chronic exposure to either the risperidone (RISP) or olanzapine (OLZ) resulted in superior effects on spatial learning performance as well as the cholinergic neurons, although the mechanism for these effects was not addressed. Objectives: The objective of this study was to investigate one plausible mechanism whereby RISP and OLZ exert superior effects on cholinergic neurons, i.e. positive effects on nerve growth factor (NGF), which is known to regulate the brain cholinergic activity as well as cognitive function. Therefore, the effects of chronic exposure to HAL, RISP, or OLZ on the expression of NGF and choline acetyltransferase (ChAT) in the hippocampus (i.e. a brain area well known to be involved in cognitive function and known to receive major cholinergic projections from the medial septum) were compared. Methods: Rats were treated with HAL (1 or 2 mg/kg per day), RISP (1.25 or 2.5 mg/kg per day), or OLZ (5 or 10 mg/kg per day) for 45 days in drinking water. NGF and ChAT were measured by immunohistochemistry and NGF protein was also measured by an enzyme-linked ImmunoSorbent assay. Results: Compared to controls, HAL exposure resulted in a marked reduction in NGF immunoreactivity in the hippocampal dentate gyrus (DG), CA1 and CA3 areas. In contrast, RISP did not alter, while OLZ significantly increased levels of NGF. These changes in NGF levels corresponded well with changes in ChAT immunoreactivity in the hippocampus and the medial septum. Conclusions: These preclinical data, combined with previously published behavioral results, support the premise that OLZ and RISP, in contrast to HAL, preserve cholinergic pathways and cognitive function via superior effects on NGF expression and are thus therapeutically superior for extended use.
PLANT PHYSIOLOGY, 2010
ROXY1 and ROXY2 are CC-type floral glutaredoxins with redundant functions in Arabidopsis (Arabido... more ROXY1 and ROXY2 are CC-type floral glutaredoxins with redundant functions in Arabidopsis (Arabidopsis thaliana) anther development. We show here that plants lacking the basic leucine-zipper transcription factors TGA9 and TGA10 have defects in male gametogenesis that are strikingly similar to those in roxy1 roxy2 mutants. In tga9 tga10 mutants, adaxial and abaxial anther lobe development is differentially affected, with early steps in anther development blocked in adaxial lobes and later steps affected in abaxial lobes. Distinct from roxy1 roxy2, microspore development in abaxial anther lobes proceeds to a later stage with the production of inviable pollen grains contained within nondehiscent anthers. Histological analysis shows multiple defects in the anther dehiscence program, including abnormal stability and lignification of the middle layer and defects in septum and stomium function. Compatible with these defects, TGA9 and TGA10 are expressed throughout early anther primordia but resolve to the middle and tapetum layers during meiosis of pollen mother cells. Several lines of evidence suggest that ROXY promotion of anther development is mediated in part by TGA9 and TGA10. First, TGA9 and TGA10 expression overlaps with ROXY1/2 during anther development. Second, TGA9/10 and ROXY1/2 operate downstream of SPOROCYTELESS/NOZZLE, where they positively regulate a common set of genes that contribute to tapetal development. Third, TGA9 and TGA10 directly interact with ROXY proteins in yeast and in plant cell nuclei. These findings suggest that activation of TGA9/10 transcription factors by ROXY-mediated modification of cysteine residues promotes anther development, thus broadening our understanding of how redox-regulated TGA factors function in plants.
Ophthalmic Epidemiology, 2006
To assess the annual number of glaucoma operations and admissions in the public sector tertiary c... more To assess the annual number of glaucoma operations and admissions in the public sector tertiary care hospitals in Pakistan. Eye departments in all 18 public tertiary care centers in the country were requested to provide data on the number of glaucoma operations and admissions during 1998. Of these, 13 hospitals agreed to participate. Eye departments&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; log books or patients&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; records were used to collect data retrospectively on the total number of eye admissions, the total number of glaucoma admissions, the type of glaucoma, and the total number and type of glaucoma operations. Glaucoma accounted for 8.1% (1,942/23,931) of all eye admissions. Open-angle glaucoma was responsible for 37.6% or 731 glaucoma admissions followed by secondary glaucoma (35.0%) and angle-closure glaucoma (18.2%). During 1998, 1,407 glaucoma-related operations were performed in the selected hospitals. The mean (+/-SD) and the median number of operations performed were 108.2 (+/-59.6) and 112 (range: 17-206), respectively. Trabeculectomies accounted for 1,043 (74.1 %) of all procedures. Their number ranged from 16 to 170 (median: 84) in the selected hospitals. We believe that the annual number of glaucoma operations performed in the public tertiary care hospitals in Pakistan is far less than required. In-depth research is therefore needed to explain if this is because of gaps in service provision or a genuine shift to medical management of glaucoma on an outpatient basis.
Ophthalmic Epidemiology, 2008
Purpose: To assess visual functioning and quality of life in a representative sample of normally ... more Purpose: To assess visual functioning and quality of life in a representative sample of normally sighted, visually impaired and cataract operated individuals aged ≥30 years in Pakistan. Methods: As part of the Pakistan National Blindness and Visual Impairment Survey, visual functioning (VF) and quality of life (QOL) questionnaires were administered to participants with presenting visual acuity less than 6/60 in either eye, aphakes/pseudophakes and a phakic sample with normal acuity (≥6/12 both eyes). Results: Of 16,507 adults included in the survey, 2329 questionnaires were administered. There were strong correlations between visual acuity and VF/QOL. Mean VF and median QOL scores in normally sighted phakic individuals were 81.1 and 88.9, respectively, but were only 34.8 and 64.9 in blind unoperated individuals. In the cataract operated population overall mean VF and median QOL scores were 49.3 and 75.0. Both VF and QOL scores were lower in operated individuals than unoperated individuals (p < 0.001). Among operated individuals, rural dwelling and illiteracy were associated with lower VF and QOL scores (p all < 0.02). Although in multivariable analysis bilateral pseudophakes had similar VF scores to bilateral aphakes they had significantly better QOL scores (p = 0.001). Conclusions: Cataract surgery in Pakistan has not led to VF and QOL scores equivalent to those in unoperated individuals with the same levels of visual acuity. The higher proportion of intraocular lens surgery in recent years is likely to improve QOL following cataract surgery. Further focus is needed on rural and illiterate populations, to ensure that they achieve comparable VF/QOL outcomes following surgery.
Ophthalmic Epidemiology, 2009
To identify children aged 0-72 months with blinding xerophthalmia in the North West Frontier Prov... more To identify children aged 0-72 months with blinding xerophthalmia in the North West Frontier Province (NWFP) and its adjoining Federally Administered Tribal Areas (FATA) in Pakistan, using a new surveillance system, and to describe socio-economic and other characteristics of reported cases. All ophthalmologists in district headquarter hospitals in NWFP and agency headquarter hospitals in FATA were requested to participate in a surveillance programme for the detection of blinding xerophthalmia (corneal xerosis, corneal ulcers, keratomalacia and corneal scars related to vitamin A deficiency) for children aged 0-72 months. The surveillance included reporting of each case of blinding xerophthalmia presenting to the participating eye units over a period of 12 months and recording their socio-economic and other related characteristics. Seventy six cases of blinding xerophthalmia were reported and there was almost no gender difference. Children came from 19 of 31 districts and agencies in NWFP and FATA with a working ophthalmologist. The commonest age at presentation was 25-48 months and almost half of them belonged to households with a monthly income of &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; Pak Rs. 1200 (US $ &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 20). Precipitating systemic illnesses were diarrhea and fever with cough in 63.2% and 56.6% cases, respectively. Almost a third of children aged &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 9 months had not been immunized against measles. A quarter of all children had not been adequately breast-fed, and 7 children (9%) had never been breastfed. Majority of the cases presented during summer and autumn months. Our surveillance data provide evidence that blinding xerophthalmia does occur in children in NWFP and its adjoining FATA. The surveillance system identified high risk age groups, systemic illnesses, seasons and community groups. The detection system detects minimal numbers of cases and it is likely that the problem is even more severe.
Neuroscience Letters, 2004
Recently, we have reported studies in rats showing that the atypical antipsychotic olanzapine (OL... more Recently, we have reported studies in rats showing that the atypical antipsychotic olanzapine (OLZ), in contrast to haloperidol (HAL), was not associated with reduction of markers of central cholinergic neurons as well as decrements in cognitive performance after chronic exposure. We compared the effect of 45 day chronic exposure of HAL (2 mg/kg per day) to OLZ (10 mg/kg per day) on brain-derived neurotrophic factor (BDNF)) and its high affinity receptor TrkB in rat hippocampus. Since the use of OLZ is presently preferred over HAL in patients, effects of its post-treatment on HAL-induced changes in the expression of BDNF and its TrkB receptor were also investigated. OLZ was administered after 45 days of HAL exposure. HAL, but not OLZ, significantly reduced the levels of BDNF in hippocampus. These changes in BDNF paralleled the levels of TrkB receptors. Furthermore, post-treatment with OLZ markedly restored the HAL treatment associated reductions in both BDNF and TrkB receptors in hippocampus. q
Journal of Surgical Research, 2009
Journal of Psychiatric Research, 2004
Previously we reported that chronic exposure to haloperidol (HAL), but not the atypical antipsych... more Previously we reported that chronic exposure to haloperidol (HAL), but not the atypical antipsychotics risperidone (RISP) or clozapine (CLOZ), resulted in reductions in brain choline acetyltransferase (ChAT) immunoreactivity and impaired water maze task performance in rats. In the present study, we compared the effects of these antipsychotic drugs on the expression of nerve growth factor (NGF) as well ChAT the in the rat cortex and nucleus basalis of Meynert (NBM) in an effort to determine the underlying mechanism for the differential drug effects observed previously. We also evaluated the effects of these compounds in a crossover design to evaluate specific neurochemical consequences of switching between typical and atypical antipsychotics, a common practice observed in the clinical setting. Male Wistar rats (250-300 g) were exposed to HAL (2.0 mg/kg/day), RISP (2.5 mg/kg/day), or CLOZ (20 mg/kg/day) for 45 days or a pre-treatment regimen consisting of administering either RISP/HAL (i.e., RISP followed by HAL) or CLOZ/HAL, or a post-treatment regimen consisting of administering: HAL/RISP or HAL/CLOZ. The duration of each treatment in the crossover study was also 45 days. NGF and ChAT immunoreactivity were measured by quantitative immunohistochemistry in some sub-cerebral cortical regions and NBM after drug exposures. NGF protein was also measured by an enzymelinked ImmunoSorbent assay (ELISA) in rat sensorimotor cortex. The results indicated that HAL (but not RISP or CLOZ) significantly reduced NGF levels in some sub-cortical regions and ChAT immunoreactivity in both cortex and NBM. However, pretreatment with CLOZ prevented the HAL-associated decreases in NGF and ChAT, while post-treatment with either RISP or CLOZ (i.e., after the administration of HAL) appeared to restore NGF and ChAT to control levels. These data indicate that antipsychotic drugs exert dissimilar effects on the levels of NGF and ChAT in the brain, which may contribute to their differential effects on cognitive function. The crossover data further suggest that certain atypical antipsychotic drugs (e.g., clozapine) may have the potential to prevent or reverse the deleterious effects of HAL on important neurochemical substrates of cognitive function.
Journal of Neuroscience Research, 2007
Basic fibroblast growth factor (bFGF) and transforming growth factor-b1 (TGF-b1) play an importan... more Basic fibroblast growth factor (bFGF) and transforming growth factor-b1 (TGF-b1) play an important role in proliferation, differentiation, and survival of malignant gliomas and in normal glial cell biology. Because of these critical roles, potential interactions between these key growth factors were investigated. We previously demonstrated that bFGF potently stimulates TGF-b1 release from rat glioma cells. The purpose of the present study was to elucidate the mechanism(s) of this regulatory effect, establish its functional importance, and examine whether it extends to nontransformed rat hypothalamic astrocytes (RHA). The results revealed that RHA express the high-affinity FGF(1-4) receptors, and similarly to glioma cells, bFGF stimulated TGF-b1 release in an isoform-specific manner. A mediatory role for ERK signaling in bFGF-induced TGF-b release was suggested by the fact that MEK1 inhibition prevented this effect. Additionally, bFGF enhanced MEK1/2 phosphorylation and ERK activation/nuclear translocation, which culminated in increased activity of AP-1-mediated gene transcription. bFGF markedly induced TGF-b1 mRNA levels in an isoform-specific manner, an effect that was dependent on MEK/ERK/AP-1 signaling. Functionally, bFGF-induced proliferation of glioma cells was attenuated by MEK/ERK inhibition or immunoneutralization of TGF-b1, suggesting that this pathway may have important implications for brain tumor progression. V V C 2007 Wiley-Liss, Inc.
Journal of Antimicrobial Chemotherapy, 2010
To compare and contrast the geographic and demographic distribution of bro beta-lactamase and ant... more To compare and contrast the geographic and demographic distribution of bro beta-lactamase and antibiotic MIC(50/90) for 1440 global Moraxella catarrhalis isolates obtained from children and adults between 2001 and 2002. One thousand four hundred and forty M. catarrhalis isolates originating from seven world regions were investigated. The isolates were recovered from 411 children &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;5 years of age and 1029 adults &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;20 years of age. PCR-restriction fragment length polymorphism (RFLP) was performed to determine bro prevalence and to distinguish between bro types. MIC values of 12 different antibiotics were determined using the CLSI (formerly NCCLS) broth microdilution method. Of the 1440 isolates, 1313 (91%) possessed the bro-1 gene and 64 (4%) possessed the bro-2 gene. Additionally, the prevalence of bro positivity between the child and adult age groups was significantly different (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001), though bro-1 and bro-2 prevalences within age groups were not significantly different. Consistently higher beta-lactam MICs were observed for M. catarrhalis isolates originating in the Far East. Significant correlations in MICs were observed for several antibiotic combinations, including all five beta-lactams with each other, and among the two quinolones. The worldwide prevalence of bro gene carriage in clinical isolates of M. catarrhalis is now approaching 95%, with children significantly more likely to harbour bro-positive isolates than adults. Further, statistically significant differences in the distribution of beta-lactam MICs were observed between different world regions, particularly with respect to the Far East.
Infection and Immunity, 2002
The attenuation and immunogenicity of two novel Salmonella vaccine strains, Salmonella enterica s... more The attenuation and immunogenicity of two novel Salmonella vaccine strains, Salmonella enterica serovar Typhi (Ty2 ⌬aroC ⌬ssaV, designated ZH9) and S. enterica serovar Typhimurium (TML ⌬aroC ⌬ssaV, designated WT05), were evaluated after their oral administration to volunteers as single escalating doses of 10 7 , 10 8 , or 10 9 CFU. ZH9 was well tolerated, not detected in blood, nor persistently excreted in stool. Six of nine volunteers elicited anti-serovar Typhi lipopolysaccharide (LPS) immunoglobulin A (IgA) antibody-secreting cell (ASC) responses, with three of three vaccinees receiving 10 8 and two of three receiving 10 9 CFU which elicited high-titer LPS-specific serum IgG. WT05 was also well tolerated with no diarrhea, although the administration of 10 8 and 10 9 CFU resulted in shedding in stools for up to 23 days. Only volunteers immunized with 10 9 CFU of WT05 mounted detectable serovar Typhimurium LPS-specific ASC responses and serum antibody responses were variable. These data indicate that mutations in type III secretion systems may provide a route to the development of live vaccines in humans and highlight significant differences in the potential use of serovars Typhimurium and Typhi.