Vladimir Gavrilov - Academia.edu (original) (raw)
Papers by Vladimir Gavrilov
Renal Failure, 2004
Objective. Study the possible excretion of vitamin A in urine of critically ill patients complica... more Objective. Study the possible excretion of vitamin A in urine of critically ill patients complicated with acute renal failure. Patients and Methods. Nine Intensive Care Unit patients, age 71.2 ± 15.7 (mean ± SD) with acute renal failure were studied. Urinary retinol, creatinine, protein, albumin, and serum creatinine were measured. Results. All patients excreted retinol in urine; individual values ranged from 0.007 to 0.379 mmol retinol/mmol creatinine. There was no correlation of urinary retinol/creatinine ratio with serum creatinine or with urinary protein/creatinine and albumin/creatinine ratios. Conclusion. Excretion of retinol in urine may be indicative of acute renal failure in critically ill patients.
Kidney International, 2006
Anticancer Research, Nov 1, 2014
Aim: To enhance the anticancer activity of vinorelbine, cisplatin and ionizing radiation (IR) com... more Aim: To enhance the anticancer activity of vinorelbine, cisplatin and ionizing radiation (IR) combination against non-small cell lung cancer (NSCLC) cells by co-administration of sodium valproate (VPA), a histone deacetylase inhibitor, and to elucidate molecular events underpinning treatment efficacy. Materials and Methods: The NSCLC A549 cell line was treated with cisplatin (0.2 μg/ml), vinorelbine (2 nM), VPA (1 mM) and IR (2.5 Gy) alone, or in combination. Cell proliferation, cellcycle distribution, apoptosis, and levels of DNA doublestrand breaks, activated DNA damage checkpoint kinases pCHK1, pCHK2, cell-cycle inhibitors p21 CIP1/WAF1 and p27 KIP1 were assessed. Results: VPA markedly enhanced the DNA-damaging effect of the cisplatin-vinorelbine-IR combination and induced increased DSBs, and expression of pCHK2, pCHK1, p21 CIP1/WAF1 and p27 KIP1. These molecular changes led to cell-cycle arrest and increased apoptosis and consequently markedly curtailed cancer cell growth. Conclusion: VPA markedly enhances the anticancer activity of cisplatin-vinorelbine-IR combination. This finding has translational implications for enhancing the efficacy of anticancer treatment and for reducing side-effects by reducing doses of radiation and drugs. Non-small cell lung cancer (NSCLC) accounts for 80%-85% of all lung cancer cases (1). A considerable number (up to 30%) of patients with NSCLC present with locally advanced, unresectable stage III disease (2). For these patients, 6565
The Israel Medical Association journal : IMAJ, 2002
The Israel Medical Association journal : IMAJ, 2001
Narcotic abuse has steadily become more prevalent in Israel and may result in an increasing numbe... more Narcotic abuse has steadily become more prevalent in Israel and may result in an increasing number of children exposed prenatally to narcotics, with a consequent increase in the number of infants born with neonatal abstinence syndrome. To report our experience with infants born to narcotic-addicted women between the years 1995 and 1998 at the Soroka University Medical Center. The medical records of 24 newborns and their drug-addicted mothers admitted to our Medical Center for parturition were analyzed retrospectively. A diagnosis of NAS was established on the basis of the clinical presentation and anamnesis. The Finnegan Neonatal Abstinence Scoring System was used to assess drug withdrawal. Urine toxicological analysis for narcotics was done only for the year 1998. Of the 24 newborn infants exposed prenatally to narcotics 23 (96%) developed NAS, and 78% (18 of the 23) had a Finnegan score of 8 or more. These 18 infants were treated pharmacologically (tincture of opium and/or phenoba...
The Israel Medical Association journal : IMAJ, 2002
Adolescent suicide has become increasingly more prevalent in recent years, with self-poisoning be... more Adolescent suicide has become increasingly more prevalent in recent years, with self-poisoning being a frequent means of suicide attempt. To investigate the factors associated with adolescent self-poisoning. Data on adolescents referred for intentional self-poisoning to the Adolescent Medical Unit during the years 1990-1998 were evaluated retrospectively. Data were obtained from the hospital medical records and included the following factors: sociodemographic data, educational status, agent and route of intake, motivation for overdose, and the extent of serious suicidal intent. We evaluated 324 cases of adolescent self-poisoners aged 12-18 years (mean +/- SD 14.8 +/- 1.5 years). The female/male ratio was 8:1. Most of the patients were attending school and lived in urban areas. Oral ingestion was the only route of intake; 84.5% of the patients ingested drugs and 10.5% non-medicinal compounds. The drug most commonly taken was acetaminophen. The non-medicinal compounds were mostly pest...
Journal of Pharmacy Technology, 2000
Objective: To formulate the tear/plasma urea ratio as a coefficient for correcting drug concentra... more Objective: To formulate the tear/plasma urea ratio as a coefficient for correcting drug concentrations in tears. Subjects and Methods: Urea concentrations were measured in 14 paired tear and plasma samples from seven healthy adult volunteers (3 women, 4 men). A second sample was obtained one hour after the first. The samples were simultaneously assayed for urea concentrations by a urease method (Boehringer Mannheim). Results: Our data show a highly significant correlation between tear and plasma urea concentrations in all the samples (r = 0.985, p < 0.001; r = 0.928, p < 0.003; and r = 0.944, p < 0.001 in the first, second, and total collection of samples, respectively). In all paired tear and plasma samples, urea content in tears was higher than in plasma (p < 0.001, p < 0.015, and p < 0.001 in the first, second, and total samples, respectively). The tear/plasma urea ratio in all samples ranged from 1.016 to 1.225 (mean ± SD 1.126 ± 0.068) and had a significant negative correlation (r = −0.538; p < 0.05) with tear volume (range 25–155 μL, mean ± SD 83.9 ± 42.6). Conclusions: Higher urea concentrations in tears than in plasma and a negative correlation between tear volume and the tear/plasma urea ratio indicate that tear evaporation and, consequently, tear concentration occur during sample collection. These data and the highly significant correlation between tear and plasma urea concentrations justify the use of the tear/plasma urea ratio as a correction coefficient for monitoring drug concentrations in tears.
In vivo (Athens, Greece)
Targeting of the epidermal growth factor receptor (EGFR) pathway is a promising treatment strateg... more Targeting of the epidermal growth factor receptor (EGFR) pathway is a promising treatment strategy for aggressive androgen-refractory prostate cancer (PCa). The effect of treating the androgen-resistant PCa cell line DU145 with a combination of the anti-EGFR drug cetuximab and 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) was evaluated. DU145 cells were treated with 5 nM cetuximab, 100 nM 1,25(OH)2D3 or a combination of both. The effect of the treatments on cell growth, cell-cycle and apoptosis was evaluated. Single-drug treatments decreased DU145 cell growth by up to 25% and caused a 1.5-to 1.7-fold increase of apoptosis, but did not affect the cell-cycle distribution. However, dual treatment with a combination of cetuximab and 1,25(OH)2D3 inhibited DU145 cell proliferation by 40%, caused considerable cell-cycle arrest in the Go/Gl-phase, and enhanced apoptosis by 2.5-fold (compared to the control, p < 0. 0001, p <0. 006 and p <0. 0001, respectively). A combination of cetuximab a...
The Journal of Steroid Biochemistry and Molecular Biology, 2010
The Journal of Trauma: Injury, Infection, and Critical Care, 2003
LF 16-0687 Ms previously was reported to improve Neurological Severity Score (NSS) and decrease c... more LF 16-0687 Ms previously was reported to improve Neurological Severity Score (NSS) and decrease cerebral edema and prostaglandin E(2) (PGE(2)) release after closed head trauma (CHT) in rats. Here, we examined whether these beneficial effects of LF 16-0687 Ms are altered when CHT is accompanied by acute ethanol administration. Six groups of rats (n = 8 per group) were examined during combination of the following experimental conditions: CHT versus sham operation, LF 16-0687 Ms 3 mg/kg subcutaneously versus saline, and ethanol 2 g/kg versus saline. After CHT, brain water content decreased and NSS improved with ethanol + LF 16-0687 Ms as compared with values after saline or ethanol. PGE(2) release decreased with ethanol (147 +/- 59 pg/mg tissue) but not with ethanol + LF 16-0687 Ms (286 +/- 194 pg/mg tissue). Ethanol does not affect the improvement of NSS and the decrease of cerebral edema seen with LF 16-0687 Ms after CHT, but does reverse the ability of LF 16-0687 Ms to minimize the increase of PGE(2) release. In intoxicated patients, bradykinin antagonist therapy may improve post-CHT outcome without altering PGE(2) release.
Journal of Pharmacy and Pharmacology, 2003
Paracetamol is a safe and effective analgesic and antipyretic agent, and is one of the most widel... more Paracetamol is a safe and effective analgesic and antipyretic agent, and is one of the most widely used medications for infants and children. The formulations currently available have been designed for oral and rectal administration. However, they are not practical in young patients with vomiting and diarrhoea, or in those who refuse to take the full dose. An alternative route of administration would be a significant contribution to the paediatric pharmacopoeia. The aim of this study was to develop a new transdermal system for optional therapeutic administration of paracetamol in infants and children. In-vivo studies were carried out in animals using a transdermal system of high-loaded, soluble paracetamol in a hydrogel patch, which was also tested in-vitro for 8 h. Although the beneficial contribution of glyceryl oleate to the transdermal penetration of paracetamol seemed to be significant in-vitro, it was shown to be insufficient in-vivo. To improve the penetration of the drug, 4%...
Current Therapeutic Research, 2003
Current Therapeutic Research, 2002
Results: The study was carried out in the clinical practices of 6 board-certified pediatricians t... more Results: The study was carried out in the clinical practices of 6 board-certified pediatricians treating a total of 9300 children in 20002001. A total of 1925 prescriptions for 160 different medications were given to 1802 children (959 boys, 843 girls, mean [SD] age, 4.8 [3.9] years). Of the ...
The Israel Medical Association journal : IMAJ, 2000
Many medications used for children have not undergone evaluation to assure acceptable standards f... more Many medications used for children have not undergone evaluation to assure acceptable standards for optimal dose, safety and efficacy. As a result, the majority of children admitted to hospital wards receive medications outside the terms of their license (off-label) or medications that are not specifically licensed for use in children (unlicensed). The extent of unlicensed and off-label medication use in ambulatory children is unknown. To determine the extent of unlicensed and off-label medication use in a general pediatrics ambulatory hospital unit in Israel. We conducted a retrospective analysis of the medical records of 132 outpatient children treated in the General Pediatrics Ambulatory Unit of the Soroka Medical Center, Beer Sheva, in November-December 1998. The children's ages ranged from 1 month to 18 years (mean +/- SD 50 +/- 58 months). Of the 222 prescriptions given to these children, one-third were unlicensed (8%) or unlabeled (26%). Different dose and age were the mo...
Renal Failure, 2004
Objective. Study the possible excretion of vitamin A in urine of critically ill patients complica... more Objective. Study the possible excretion of vitamin A in urine of critically ill patients complicated with acute renal failure. Patients and Methods. Nine Intensive Care Unit patients, age 71.2 ± 15.7 (mean ± SD) with acute renal failure were studied. Urinary retinol, creatinine, protein, albumin, and serum creatinine were measured. Results. All patients excreted retinol in urine; individual values ranged from 0.007 to 0.379 mmol retinol/mmol creatinine. There was no correlation of urinary retinol/creatinine ratio with serum creatinine or with urinary protein/creatinine and albumin/creatinine ratios. Conclusion. Excretion of retinol in urine may be indicative of acute renal failure in critically ill patients.
Kidney International, 2006
Anticancer Research, Nov 1, 2014
Aim: To enhance the anticancer activity of vinorelbine, cisplatin and ionizing radiation (IR) com... more Aim: To enhance the anticancer activity of vinorelbine, cisplatin and ionizing radiation (IR) combination against non-small cell lung cancer (NSCLC) cells by co-administration of sodium valproate (VPA), a histone deacetylase inhibitor, and to elucidate molecular events underpinning treatment efficacy. Materials and Methods: The NSCLC A549 cell line was treated with cisplatin (0.2 μg/ml), vinorelbine (2 nM), VPA (1 mM) and IR (2.5 Gy) alone, or in combination. Cell proliferation, cellcycle distribution, apoptosis, and levels of DNA doublestrand breaks, activated DNA damage checkpoint kinases pCHK1, pCHK2, cell-cycle inhibitors p21 CIP1/WAF1 and p27 KIP1 were assessed. Results: VPA markedly enhanced the DNA-damaging effect of the cisplatin-vinorelbine-IR combination and induced increased DSBs, and expression of pCHK2, pCHK1, p21 CIP1/WAF1 and p27 KIP1. These molecular changes led to cell-cycle arrest and increased apoptosis and consequently markedly curtailed cancer cell growth. Conclusion: VPA markedly enhances the anticancer activity of cisplatin-vinorelbine-IR combination. This finding has translational implications for enhancing the efficacy of anticancer treatment and for reducing side-effects by reducing doses of radiation and drugs. Non-small cell lung cancer (NSCLC) accounts for 80%-85% of all lung cancer cases (1). A considerable number (up to 30%) of patients with NSCLC present with locally advanced, unresectable stage III disease (2). For these patients, 6565
The Israel Medical Association journal : IMAJ, 2002
The Israel Medical Association journal : IMAJ, 2001
Narcotic abuse has steadily become more prevalent in Israel and may result in an increasing numbe... more Narcotic abuse has steadily become more prevalent in Israel and may result in an increasing number of children exposed prenatally to narcotics, with a consequent increase in the number of infants born with neonatal abstinence syndrome. To report our experience with infants born to narcotic-addicted women between the years 1995 and 1998 at the Soroka University Medical Center. The medical records of 24 newborns and their drug-addicted mothers admitted to our Medical Center for parturition were analyzed retrospectively. A diagnosis of NAS was established on the basis of the clinical presentation and anamnesis. The Finnegan Neonatal Abstinence Scoring System was used to assess drug withdrawal. Urine toxicological analysis for narcotics was done only for the year 1998. Of the 24 newborn infants exposed prenatally to narcotics 23 (96%) developed NAS, and 78% (18 of the 23) had a Finnegan score of 8 or more. These 18 infants were treated pharmacologically (tincture of opium and/or phenoba...
The Israel Medical Association journal : IMAJ, 2002
Adolescent suicide has become increasingly more prevalent in recent years, with self-poisoning be... more Adolescent suicide has become increasingly more prevalent in recent years, with self-poisoning being a frequent means of suicide attempt. To investigate the factors associated with adolescent self-poisoning. Data on adolescents referred for intentional self-poisoning to the Adolescent Medical Unit during the years 1990-1998 were evaluated retrospectively. Data were obtained from the hospital medical records and included the following factors: sociodemographic data, educational status, agent and route of intake, motivation for overdose, and the extent of serious suicidal intent. We evaluated 324 cases of adolescent self-poisoners aged 12-18 years (mean +/- SD 14.8 +/- 1.5 years). The female/male ratio was 8:1. Most of the patients were attending school and lived in urban areas. Oral ingestion was the only route of intake; 84.5% of the patients ingested drugs and 10.5% non-medicinal compounds. The drug most commonly taken was acetaminophen. The non-medicinal compounds were mostly pest...
Journal of Pharmacy Technology, 2000
Objective: To formulate the tear/plasma urea ratio as a coefficient for correcting drug concentra... more Objective: To formulate the tear/plasma urea ratio as a coefficient for correcting drug concentrations in tears. Subjects and Methods: Urea concentrations were measured in 14 paired tear and plasma samples from seven healthy adult volunteers (3 women, 4 men). A second sample was obtained one hour after the first. The samples were simultaneously assayed for urea concentrations by a urease method (Boehringer Mannheim). Results: Our data show a highly significant correlation between tear and plasma urea concentrations in all the samples (r = 0.985, p < 0.001; r = 0.928, p < 0.003; and r = 0.944, p < 0.001 in the first, second, and total collection of samples, respectively). In all paired tear and plasma samples, urea content in tears was higher than in plasma (p < 0.001, p < 0.015, and p < 0.001 in the first, second, and total samples, respectively). The tear/plasma urea ratio in all samples ranged from 1.016 to 1.225 (mean ± SD 1.126 ± 0.068) and had a significant negative correlation (r = −0.538; p < 0.05) with tear volume (range 25–155 μL, mean ± SD 83.9 ± 42.6). Conclusions: Higher urea concentrations in tears than in plasma and a negative correlation between tear volume and the tear/plasma urea ratio indicate that tear evaporation and, consequently, tear concentration occur during sample collection. These data and the highly significant correlation between tear and plasma urea concentrations justify the use of the tear/plasma urea ratio as a correction coefficient for monitoring drug concentrations in tears.
In vivo (Athens, Greece)
Targeting of the epidermal growth factor receptor (EGFR) pathway is a promising treatment strateg... more Targeting of the epidermal growth factor receptor (EGFR) pathway is a promising treatment strategy for aggressive androgen-refractory prostate cancer (PCa). The effect of treating the androgen-resistant PCa cell line DU145 with a combination of the anti-EGFR drug cetuximab and 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) was evaluated. DU145 cells were treated with 5 nM cetuximab, 100 nM 1,25(OH)2D3 or a combination of both. The effect of the treatments on cell growth, cell-cycle and apoptosis was evaluated. Single-drug treatments decreased DU145 cell growth by up to 25% and caused a 1.5-to 1.7-fold increase of apoptosis, but did not affect the cell-cycle distribution. However, dual treatment with a combination of cetuximab and 1,25(OH)2D3 inhibited DU145 cell proliferation by 40%, caused considerable cell-cycle arrest in the Go/Gl-phase, and enhanced apoptosis by 2.5-fold (compared to the control, p < 0. 0001, p <0. 006 and p <0. 0001, respectively). A combination of cetuximab a...
The Journal of Steroid Biochemistry and Molecular Biology, 2010
The Journal of Trauma: Injury, Infection, and Critical Care, 2003
LF 16-0687 Ms previously was reported to improve Neurological Severity Score (NSS) and decrease c... more LF 16-0687 Ms previously was reported to improve Neurological Severity Score (NSS) and decrease cerebral edema and prostaglandin E(2) (PGE(2)) release after closed head trauma (CHT) in rats. Here, we examined whether these beneficial effects of LF 16-0687 Ms are altered when CHT is accompanied by acute ethanol administration. Six groups of rats (n = 8 per group) were examined during combination of the following experimental conditions: CHT versus sham operation, LF 16-0687 Ms 3 mg/kg subcutaneously versus saline, and ethanol 2 g/kg versus saline. After CHT, brain water content decreased and NSS improved with ethanol + LF 16-0687 Ms as compared with values after saline or ethanol. PGE(2) release decreased with ethanol (147 +/- 59 pg/mg tissue) but not with ethanol + LF 16-0687 Ms (286 +/- 194 pg/mg tissue). Ethanol does not affect the improvement of NSS and the decrease of cerebral edema seen with LF 16-0687 Ms after CHT, but does reverse the ability of LF 16-0687 Ms to minimize the increase of PGE(2) release. In intoxicated patients, bradykinin antagonist therapy may improve post-CHT outcome without altering PGE(2) release.
Journal of Pharmacy and Pharmacology, 2003
Paracetamol is a safe and effective analgesic and antipyretic agent, and is one of the most widel... more Paracetamol is a safe and effective analgesic and antipyretic agent, and is one of the most widely used medications for infants and children. The formulations currently available have been designed for oral and rectal administration. However, they are not practical in young patients with vomiting and diarrhoea, or in those who refuse to take the full dose. An alternative route of administration would be a significant contribution to the paediatric pharmacopoeia. The aim of this study was to develop a new transdermal system for optional therapeutic administration of paracetamol in infants and children. In-vivo studies were carried out in animals using a transdermal system of high-loaded, soluble paracetamol in a hydrogel patch, which was also tested in-vitro for 8 h. Although the beneficial contribution of glyceryl oleate to the transdermal penetration of paracetamol seemed to be significant in-vitro, it was shown to be insufficient in-vivo. To improve the penetration of the drug, 4%...
Current Therapeutic Research, 2003
Current Therapeutic Research, 2002
Results: The study was carried out in the clinical practices of 6 board-certified pediatricians t... more Results: The study was carried out in the clinical practices of 6 board-certified pediatricians treating a total of 9300 children in 20002001. A total of 1925 prescriptions for 160 different medications were given to 1802 children (959 boys, 843 girls, mean [SD] age, 4.8 [3.9] years). Of the ...
The Israel Medical Association journal : IMAJ, 2000
Many medications used for children have not undergone evaluation to assure acceptable standards f... more Many medications used for children have not undergone evaluation to assure acceptable standards for optimal dose, safety and efficacy. As a result, the majority of children admitted to hospital wards receive medications outside the terms of their license (off-label) or medications that are not specifically licensed for use in children (unlicensed). The extent of unlicensed and off-label medication use in ambulatory children is unknown. To determine the extent of unlicensed and off-label medication use in a general pediatrics ambulatory hospital unit in Israel. We conducted a retrospective analysis of the medical records of 132 outpatient children treated in the General Pediatrics Ambulatory Unit of the Soroka Medical Center, Beer Sheva, in November-December 1998. The children's ages ranged from 1 month to 18 years (mean +/- SD 50 +/- 58 months). Of the 222 prescriptions given to these children, one-third were unlicensed (8%) or unlabeled (26%). Different dose and age were the mo...