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Biomedical subjects

F Jamali

Publications and source records attributed to F Jamali.

At least 19 recordsLinked to original sources
PubMed2006

Solid pseudopapillary neoplasm of the pancreas in a 12-year-old female: case report and review of the literature.

Solid pseudopapillary neoplasms of the pancreas (SPNP) are rare pancreatic tumors that occur predominantly in young women, with very few cases reported in men. While the origin of the tumor may be unclear, it is characterized by a distinct histological appearance and a clinical course highlighting its low malignant potential. SPNP have an excellent prognosis and are potentially curable provided they are managed appropriately by complete surgical resection. In the rare instances where metastatic disease is encountered, surgical debulking has been shown to prolong survival. The role of chemotherapy and radiation therapy in the management of SPNP is still controversial. We report here on an unusual occurrence of SPNP in the area of the head of the pancreas in a 12-year-old female treated by pancreatico-duodenectomy, together with a review of the literature.

Child↗
PubMed2004

Biological control of chickpea Fusarium wilt by antagonistic bacteria under greenhouse condition.

In this survey, Fusarium oxysporum was isolated from roots infected plants and was shown to be pathogenic. Experiment were carried out with seven antagonistic bacteria. Based on biochemical, Physiological and morphological tests, isolates B-120, B-32, B-28 and B-22 were identified as Bacillus subtilis and isolates Pf-100, Pf-10 and CHAO as Pseudomonas fluorescens. In greenhouse studies, only isolate B-120 (Less than benomyl) reduced Fusarium wilt of chickpea in both seed and soil treatments. The application of antagonistic bacteria had no different effects on plant growth factors. Soil treatment of bacteria had a better effects on plant growth than that of bacterial seed treatment. The use of antagonists (B-120, B-28, B-120 and CHAO) in combination had no significant effect on plant growth factors and reduction wilt disease than that each isolate was applied individually.

Bacillus subtilis↗
PubMed2003

Laparoscopic total mesorectal excision (TME) for rectal cancer surgery: long-term outcomes.

BACKGROUND: Total mesorectal excision (TME) offers the lowest reported rates of local recurrence and the best survival results in patients with rectal cancer. However, the laparoscopic approach to resection for colorectal cancer remains controversial due to fears that oncologic principles will be compromised. We assessed the feasibility, safety and long-term outcome of laparoscopic rectal cancer resections following the principles of TME. The aim of this study was to evaluate the perioperative outcome and long-term results of laparoscopic TME. METHODS: We reviewed the prospective database of 102 consecutive unselected patients undergoing laparoscopic TME for rectal cancer between November 1991 and December 2000. Follow-up was done through office charts or direct patient contact. Recurrence and survival curves were generated by the Kaplan-Meier method. RESULTS: Laparoscopic TME was completed successfully in 99 patients, whereas conversion to an open approach was required in three cases (3%). The overall morbidity and mortality rates were 27% and 2%, respectively, with an overall anastomotic leak rate of 17%. Of the 102 patients, four were excluded from the oncologic evaluation because final pathology was not confirmatory (two had anal canal squamous cell carcinoma and two had villous adenoma with dysplasia). In 90 of the 98 remaining patients (91.8%), the resection was considered curative. The remainder had a palliative resection due to synchronous metastatic disease or locally advanced disease. Mean follow-up was 36 months (range, 6-96). There were no trocar site recurrences. The local recurrence rate was 6%, and the cancer-specific survival of all curatively resected patients was 75% at 5 years. The overall survival rate of all curatively resected patients was 65% at 5 years; mean survival time was 6.23 years (95% confidence interval [CI], 5.39-7.07). CONCLUSION: Laparoscopic TME is feasible and safe. The laparoscopic approach to the surgical treatment of operable rectal cancer does not seem to entail any oncologic disadvantages.

Adult↗
PubMed2001

Therapeutic relevance of altered cytokine expression.

Cytokines and their receptors have numerous physiological functions. Altered concentrations of these mediators are associated with various afflictions. For example, over-expression of cytokines has been associated with altered drug concentrations and activity. Greater concentrations of cardiovascular drugs have been observed in humans and laboratory animals with various types of inflammatory disorders compared to healthy controls. Interestingly, the observed higher concentrations of drugs such as propranolol and verapamil have not been associated with increased effects. Indeed, reduced response to these cardiovascular drugs is observed, suggestive of cytokine-mediated downregulation of receptors. Increased cytokine concentrations have also been associated with decreased response to drugs used in treatment of other disorders such as AIDS, asthma and psychiatric diseases. This reduced response to drug in the presence of altered cytokine concentrations is especially relevant to the elderly population which has a greater incidence of multiple diseases and elevated concentrations of various cytokines compared to younger individuals. Furthermore, inflammatory conditions and their accompanied increased over-expression of cytokines are suggested to be the main determinants of therapeutic failure in myocardial infarction and angina. Therefore, altered cytokine concentrations may influence therapeutic outcomes of pharmacotherapy and result in treatment failure.

Cytokines↗
PubMed2001

Safety of laparoscopic approach for acute cholecystitis: retrospective study of 609 cases.

Laparoscopic cholecystectomy (LC) is now widely accepted as the modality of choice for the treatment of symptomatic uncomplicated cholelithiasis. The application of the laparoscopic technique in the setting of acute cholecystitis (AC) is more controversial. The precise role as well as the potential benefits of LC in the treatment of the acutely inflamed gallbladder have not been clearly established through large clinical series. The aim of our study was to assess the feasibility, safety, benefits, and specific complications of the laparoscopic approach in patients with AC. A retrospective chart analysis involving the patients admitted to two busy emergency digestive surgical units between October 1990 and December 1997 was carried out. Six hundred and nine patients meeting our criteria for AC were identified and evaluated. Overall complication rate was 15% with 12 postoperative bile leakages (1.97%) and 4 biliary tract injuries (BTI) (0.66%). The overall mortality rate was 0.66%. Local and overall complication rates were significantly correlated with the delay between the onset of acute symptoms and the operation but not the rate of general complications nor deaths. Our results demonstrate the safety and feasibility of LC in the setting of AC. Early cholecystectomy within 4 days is strongly recommended to minimize complications and increase the chances of a successful laparoscopic approach.

Acute Disease↗
PubMed2001

Drug-disease interactions: reduced beta-adrenergic and potassium channel antagonist activities of sotalol in the presence of acute and chronic inflammatory conditions in the rat.

Inflammation may influence response to pharmacotherapy. We investigated the effect of inflammation on response to sotalol, a beta-adrenergic receptor and potassium channel antagonist. Racemic sotalol (40 mg kg(-1)) was administered to healthy, acutely (interferonalpha 2a-induced) and chronically (Mycobacterium butyricum-induced adjuvant arthritis) inflamed male Sprague-Dawley rats (n=4 - 6/group). Another group of interferon-treated rats received 3 mg kg(-1) of anti-TNF antibody infliximab. Electrocardiogram (ECG) recorded and plasma sotalol concentration monitored for 6 h. The study was repeated in acutely inflamed rats following administration of stereochemically pure individual sotalol enantiomers [40 mg kg(-1) S (potassium channel blocker) or 20 mg kg(-1) R (beta-adrenergic/potassium channel blocker)]. Chronic arthritis was readily evident. Acute arthritis was associated with elevated segmented neutrophils and increased plasma nitrite and tumour necrosis factor (TNF) concentrations. Sotalol affected ECG in all rats. In both inflamed groups, however, response to sotalol in prolongation of QT interval (potassium channel sensitivity) was reduced. The effect of PR interval (beta-adrenergic activity) was also reduced following administration of the racemate and R-enantiomer. No significant differences in pharmacokinetics were observed between control and inflamed rats. Infliximab reduced nitrite and TNF concentrations and reversed the effect of acute inflammation on both PR and QT intervals. The reduced electrocardiographic responses to sotalol is likely due to the influence of inflammation on the action of the drug on both beta-adrenergic and potassium channel receptors secondary to over-expression of pro-inflammatory cytokines and/or nitric oxide. Our observation may have therapeutic consequences in all conditions where inflammatory mediators are increased.

Acute Disease↗
PubMed2001

Telerobotic laparoscopic cholecystectomy: initial clinical experience with 25 patients.

OBJECTIVE: To determine the safety and feasibility of performing telerobotic laparoscopic cholecystectomies. This will serve as a preliminary step toward the integration of computer-rendered three-dimensional preoperative imaging studies of anatomy and pathology onto the patient's own anatomy during surgery. SUMMARY BACKGROUND DATA: Computer-assisted surgery (CAS) increases the surgeon's dexterity and precision during minimally invasive surgery, especially when using microinstruments. Clinical trials have shown the improved microsurgical precision afforded by CAS in the minimally invasive setting in cardiac and gynecologic surgery. Future applications would allow integration of preoperative data and augmented-reality simulation onto the actual procedure. METHODS: Beginning in September 1999, CAS was used to perform cholecystectomies on 25 patients at a single medical center in this nonrandomized, prospective study. The operations were performed by one of two surgeons who had previous laboratory experience using the computer interface. The entire dissection was performed by the surgeon, who remained at a distance from the patient but in the same operating room. The operation was evaluated according to time of dissection, time of assembly/disassembly of robot, complications, immediate postoperative course, and short-term follow-up. RESULTS: Twenty of the 25 patients had symptomatic cholelithiasis, 1 had a gallbladder polyp, and 4 had acute cholecystitis. Twenty-four of the 25 laparoscopic cholecystectomies were successfully completed by CAS. There was one conversion to conventional laparoscopic cholecystectomy. Set-up and takedown of the robotic arms took a median of 18 minutes. The median operative time for dissection and the overall operative time were 25 and 108 minutes, respectively. There were no intraoperative complications. There was one postoperative complication of a suspected pulmonary embolus, which was treated with anticoagulation. All patients were tolerating diet at discharge. CONCLUSIONS: Laparoscopic cholecystectomy performed by CAS is safe and feasible, with operative times and patient recovery similar to those of conventional laparoscopy. At present, CAS cholecystectomy offers no obvious advantages to patients, but the potential advantages of CAS lie in its ability to convert the surgical act into digitized data. This digitized format can then interface with other forms of digitized data, such as pre- or intraoperative imaging studies, or be transmitted over a distance. This has the potential to revolutionize the way surgery is performed.

Acute Disease↗
PubMed2001

Misoprostol therapeutics revisited.

Misoprostol, a prostaglandin E1 analog, is a racemate of four stereoisomers. On administration it rapidly de-esterifies to its active form, misoprostolic acid. Misoprostolic acid is 85% albumin bound and has a half-life of approximately 30 minutes. It is excreted in urine as inactive metabolites. No significant drug interactions have been reported. Besides its gastrointestinal protective and uterotonic activities, misoprostol regulates various immunologic cascades. It inhibits platelet-activating factor and leukocyte adherence, and modulates adhesion molecule expression. It protects against gut irradiation injury, experimental gastric cancer, enteropathy, and constipation. It improves nutrient absorption in cystic fibrosis. Misoprostol has utility in acetaminophen and ethanol hepatotoxicity, hepatitis, and fibrosis. It is effective in asthmatics and aspirin-sensitive asthmatic and allergic patients. It lowers cholesterol and severity of peripheral vascular diseases, prolongs survival of cardiac and kidney transplantation, synergizes cyclosporine, and protects against cyclosporine-induced renal damage. It works against drug-induced renal damage, interstitial cystitis, lupus nephritis, and hepatorenal syndrome. It is useful in periodontal disease and dental repair. Misoprostol enhances glycosoaminoglycan synthesis in cartilage after injury. It prevents ultraviolet-induced cataracts and reduces intraocular pressure in glaucoma and ocular hypertension. It synergizes antiinflammatory and analgesic effects of diclofenac or colchicine and has been administered to treat trigeminal neuralgic pain. It reduces chemotherapy-induced hair loss and recovery time from burn injury, and is effective in treating sepsis, multiple sclerosis, and pancreatitis.

Animals↗
PubMed2000

Decreased dromotropic response to verapamil despite pronounced increased drug concentration in rheumatoid arthritis.

AIMS: Inflammation reduces hepatic clearance of many drugs with unknown therapeutic consequences. This study was carried out to examine the effect of rheumatoid arthritis (RA) on the pharmacokinetics and pharmacodynamics of verapamil. METHODS: Eight RA patients were age- and sex-matched with eight healthy volunteers. The disease severity was assessed, and ECG, blood pressure and verapamil enantiomers concentrations were measured for 12 h post 80 mg oral verapamil. Serum interleukin-6 (IL-6) and nitrite (NO2-) were measured in predose samples. RESULTS: IL-6 and NO2- concentrations were significantly increased in parallel with disease severity. Oral clearance of both S- and R-verapamil was significantly decreased by RA. While the unbound fraction of S- and R-verapamil decreased by 5 and 7-fold, respectively, the unbound AUC remained unchanged for the more potent enantiomer, S-verapamil. AUC of norverapamil enantiomers was increased 2-3-fold. Despite elevated serum drug concentrations in RA, the potential to prolong the PR-interval was significantly reduced by one fold and the effect on the heart rate and blood pressure did not increase. CONCLUSIONS: RA results in increased verapamil concentrations due likely to changes in protein binding, decreased clearance and/or altered hepatic blood flow. A significant decrease in dromotropic effect, despite increased serum drug concentrations, may be attributed to receptor down regulation caused by pro-inflammatory cytokines and/or NO.

Adult↗
PubMed2000

[Surgical treatment of acute sigmoiditis].

Virtually unknown at the beginning of the century, diverticulosis has become very prevalent in western countries. The natural history of the disease is notable for its acute, sometimes recurrent, attacks of diverticulitis and the significant risk of serious complications : abscess, fistula, peritonitis. CT scanning predominates in the diagnostic evaluation. It can provide both diagnostic and prognostic information. Most mild attacks of diverticulitis respond well to medical therapy while surgical treatment is indicated in the complicated forms of the disease. Surgical therapy has gradually evolved from a complicated three stage approach to two-staged, single-staged, or even minimally invasive procedures. The current trend is to intervene surgically well after the resolution of the acute attack. To achieve this, liberal use of percutaneous drainage of collections and medical treatment are advocated. The decision to perform prophylactic sigmoid resection must be based on a balance assessment of risk factors including age, severity of attacks and their recurrence.

Acute Disease↗
PubMed1999

Stereospecific pharmacokinetics and toxicodynamics of ketorolac after oral administration of the racemate and optically pure enantiomers to the rat.

To determine the stereospecific pharmacokinetics and gastrointestinal permeability (GI) changes (surrogate measures of toxicity) in the rat following oral administration of S, R, and racemic ketorolac (KT), optically pure enantiomers (S and R 2.5 mg/kg), and racemic KT (5 mg/kg) were administered orally to male Sprague-Dawley rats and plasma samples were collected for 6 h post-dose for pharmacokinetic assessments. KT-induced changes in GI permeability were assessed using sucrose and 51Cr-EDTA as markers of gastroduodenal and distal intestinal permeability, respectively. After the racemate, R-KT was predominant in plasma (AUC S/R, 0.45). No significant differences in pharmacokinetic indices were evident following administration of the racemate as compared with individual enantiomers. In plasma, there was only negligible S-KT after administration of R-KT. After S-KT, on the other hand, AUC of R-KT was found to be 6.7% of that of S-KT. Both permeability markers showed considerable interanimal variability. Gastroduodenal permeability was significantly increased from baseline by the racemate but not by either of the two enantiomers administered alone. Permeability to 51Cr-EDTA was not significantly increased above baseline for any of the treatments. The plasma concentration of R-KT found after administration of S-KT may be from the < 2% chiral impurity which appears magnified due to its slower clearance as compared with its antipode. There is no evidence of a pharmacokinetic interaction between the enantiomers. Since 2.5 mg/kg S-KT is somewhat less toxic on the gastroduodenum than 5 mg/kg racemate, it may be a safer alternative to the latter, at least in the rat model.

Animals↗
PubMed1999

Inhibition of insulin metabolism by hydroxychloroquine and its enantiomers in cytosolic fraction of liver homogenates from healthy and diabetic rats.

To elucidate the mechanism by which hydroxychloroquine (HCQ) affects glucose metabolism, the effect of this drug and its enantiomers on insulin metabolism was studied using the cytosolic fraction of liver homogenates from healthy and diabetic rats. Eadie-Hofstee plots were monophasic suggesting that only a one-component enzyme system is involved in insulin degradation in the fraction used. Reaction velocity (V) vs substrate concentration plots were consistent with a Vmax model. HCQ caused a significant reduction in Vmax and Vmax/Km values in both healthy (Vmax, 3.63 +/- 0.46 vs 1.97 +/- 0.13, ng/min/mg; protein P < 0.001; and Vmax/Km 0.265 +/- 0.015 vs 0.112 +/- 0.004, ml/min/g protein) and diabetic rats (Vmax, 0.718 +/- 0.06 vs 0.360 +/- 0.024, ng/min/mg protein; and Vmax/Km, 0.05 +/- 0.002 vs 0.023 +/- 0.001, ml/min/g protein). Significant reduction in the V was observed in the presence of racemic (rac)-, R-, or S-HCQ. Ranking of the inhibitory potency was HCQ > S = R except at highest examined concentration (20 mg/mL) which was HCQ > S > R. In conclusion, the effect of HCQ on insulin degradation appears to be, in part, through inhibition of cytosolic insulin metabolizing enzyme. The effect is not stereoselective except at high concentrations. The R- and S-HCQ may have synergistic effects on inhibition of insulin degradation.

Animals↗
PubMed1999

Dependency of gastrointestinal toxicity on release rate of tiaprofenic acid: a novel pharmacokinetic-pharmacodynamic model.

PURPOSE: To test the hypothesis that modification of release pattern of nonsteroidal anti-inflammatory drugs (NSAIDs) formulations shifts gastrointestinal (GI) toxicity of the drugs from the upper GI region to the distal intestine. METHODS: We assessed tiaprofenic acid (TA)-induced upper and lower increased GI permeability (a surrogate marker of toxicity) after administration of 20 mg and 40 mg/kg regular release (powder) and modified release formulations [sustained release (SR) beads and diethyl-beta-cyclodextrin (DCD):TA inclusion complex (INC)]. Urinary excretion of oral doses of GI permeability probes sucrose and 51Cr-EDTA was determined as measures of gastroduodenal and distal intestine, respectively. Pharmacokinetics of TA enantiomers were also studied following administration of a single 20 mg/kg dose of racemic TA as oral SR beads and iv solution. For powder and INC, previously reported pharmacokinetic data were used. RESULTS: Regular powder significantly increased the permeability at the gastroduodenal level. Modified-release formulations, on the other hand, did not cause damage in the gastroduodenum but produced significant increase in the permeability of the lower intestine. Consequently, to assess the pharmacokinetic-pharmacodynamic relationship, a new model was developed in which contribution of toxicity resulted from direct exposure to the drug was considered. CONCLUSIONS: Since the observed site of GI damage corresponds to the site of release and absorption of NSAID from the formulation, the possibility of a shift in the site of damage must be considered for the modified release formulations. A parallel evaluation of upper and lower GI toxicity is essential for a complete assessment of NSAID-induced GI damage.

Administration, Oral↗
PubMed1999

Effects of hyperlipidemia on the pharmacokinetics of nifedipine in the rat.

PURPOSE: The effect of hyperlipidemia on nifedipine pharmacokinetics was studied. The mechanisms by which hyperlipidemia affects pharmacokinetics of drugs are mainly undetermined. Hyperlipidemia may decrease the fraction of unbound drug in plasma and/or decrease intrinsic ability of the cytochrome P-450 systems due to excess membrane cholesterol. Hyperlipidemia is a primary risk factor for coronary artery disease leading to hypertension and ischemic heart disease, for which nifedipine, a calcium channel blocker, is used. METHODS: Poloxamer 407 (P407)-induced hyperlipidemic rat model was used to study the effects of hyperlipidemia on the pharmacokinetics of nifedipine (6 mg kg-1 given i.v., i.p. and p.o.). Total plasma cholesterol levels increased from 0.82-2.02 to 5.27-11.05 mmol L-1 48 h post P407 administration (1 g kg-1, i.p.). Protein binding studies were conducted by an ultrafiltration method. RESULTS: Hyperlipidemia significantly decreased CLTB by 38% and CLTB/F by 45 and 42% following po and i.p. doses, respectively, thereby increasing AUC0-infinity, Cmax and half-life. Absolute bioavailability and Vdss remained unchanged. AUC0-infinity was affected to the same extent in each route of administration, therefore, the effect was mainly systemic rather than presystemic. Hyperlipidemia significantly lowered the fraction unbound in plasma by approximately 31%. CONCLUSIONS: The altered pharmacokinetics of nifedipine by P407-induced HYPERLIPIDEMIA may be, at least in part, due to the decrease in fraction unbound in plasma. A decrease in intrinsic clearance, however, cannot be ruled out.

Animals↗
PubMed1999

Pain-mediated altered absorption and metabolism of ibuprofen: an explanation for decreased serum enantiomer concentration after dental surgery.

AIMS: Rapid onset of analgesia is essential in the treatment of acute pain. There is evidence that conditions of stress cause delayed and decreased pain relief from oral analgesic products through impaired absorption. The aim was to determine the effect of surgery for removal of wisdom teeth on the plasma concentration-time profile of ibuprofen enantiomers. METHODS: Racemic ibuprofen, 200 mg in one group (n=7) and 600 mg in another group (n=7) was administered 1 week before (control) and again after (test) surgical removal of wisdom teeth. Serum concentrations of ibuprofen enantiomers were measured for 6 h. RESULTS: During the control phase, S- and R-ibuprofen concentrations were within the suggested therapeutic range. Surgery resulted in a 2 h delay in the mean time to peak concentration, significant decreases in serum ibuprofen concentration following both doses, and a fall to sub-optimal serum concentrations following the 200 mg dose. During the first 2 h after the 200 mg dose, dental extraction resulted in a significant reduction of the area under serum drug concentration (AUC (0, 2 h) mg l-1 h) from 5.6+/-2.9 to 1.6+/-1.8 (P<0.01) and from 5.5+/-3.0 to 2.1+/-2.0 (P<0.05) for S and R-ibuprofen, respectively. Similar observations were made following the 600 mg dose for AUC (0, 2 h) of S-ibuprofen (from 14.2+/-6.1 to 7.2+/-5.5 mg l-1 h, P<0.05) with no significant difference for R-ibuprofen (from 14.4+/-9.5 to 5.8+/-7. 1). AUC (0, 6 h) was also significantly reduced by surgery. The pattern of stereoselectivity in serum ibuprofen concentration was reversed by surgery such that the S enantiomer was predominant in the control phase but not in the post-surgery phase, which is suggestive of reduced metabolic chiral inversion. CONCLUSIONS: Surgery for wisdom tooth removal resulted in substantial decreases in the serum concentration of ibuprofen enantiomers and a prolongation in the time to peak concentration. Reduced absorption and altered metabolism are the likely cause of these changes. Thus, dental patients may experience a delayed response and possible treatment failure when taking ibuprofen for pain relief after surgery. Our observation may have implications for the treatment of other diseases.

Adult↗
PubMed1999

Pharmacokinetics and pharmacodynamics of nifedipine in untreated and atorvastatin-treated hyperlipidemic rats.

Nifedipine, a hypertensive calcium channel blocker, is commonly administered to subjects with coronary heart disease who often exhibit hyperlipidemia. In general, the pharmacokinetic consequences of hyperlipidemia include increased total drug concentrations and decreased unbound fraction in plasma. However, the pharmacodynamic consequences of hyperlipidemia are conflicting; unaltered, increased, or decreased pharmacological effects are reported. In this study, the effect of experimental hyperlipidemia on pharmacokinetic and pharmacodynamic consequences of nifedipine was studied. After establishing a dose (0.05-0.3 mg.kg(-1))-effect relationship, single 0.1 mg.kg(-1) i.v. doses of nifedipine were administered to control and poloxamer 407-induced hyperlipidemic (with and without cholesterol-lowering agent atorvastatin) rats. Mean arterial pressure, total as well as unbound nifedipine plasma concentrations, and total cholesterol were monitored. Hyperlipidemia significantly decreased systemic clearance of nifedipine by 40% and increased T(1/2) and area under the plasma concentration-time curve by 85 and 65%, respectively. Compared with the hyperlipidemic group, atorvastatin-treated rats had significantly lower total plasma cholesterol (0-70%), increased systemic clearance (39%), and decreased T(1/2) (27%) and area under the plasma concentration-time curve (24%). Hyperlipidemia prolonged pharmacological T(1/2) of nifedipine by 300%. Atorvastatin treatment significantly reduced this prolongation to 46%. There was a significant correlation between mean blood pressure and the total but not unbound nifedipine plasma concentrations. Hyperlipidemia potentiates the hypotensive effect of nifedipine by increasing its total plasma concentrations despite decreased unbound drug concentration.

Animals↗
PubMed1999

Insulin-sparing effect of hydroxychloroquine in diabetic rats is concentration dependent.

To study the effect of hydroxychloroquine (HCQ) on glucose and insulin homeostasis, healthy rats were dosed with 160 mg x kg (-1) x day(-1) of HCQ orally, and streptozocin-induced diabetic rats received 80, 120, and 160 mg x kg(-1) x day(-1) of HCQ, while controls received normal saline. Ten days after treatment with HCQ, healthy animals were challenged intravenously with insulin or glucose, while diabetic rats were given only an i.v. injection of insulin. In healthy rats, the areas within and under the glucose concentration - time curve following insulin and glucose challenge were estimated. In diabetic animals, the areas under the curve for both the percent change in serum glucose from baseline (AUG) and the percent change in serum insulin from baseline (AUI) were used as pharmacodynamic end points. In healthy rats, HCQ did not influence fasting serum glucose concentrations or glycemic profiles following i.v. administration of glucose or insulin. In diabetic rats, AUG and AUI were increased dependent on blood HCQ concentrations. The normal homeostatic mechanisms responsible for insulin-glucose regulation may compensate for possible HCQ-induced reduction of insulin metabolism in healthy rats. The HCQ dose- or concentration-effect relationships for glucose and insulin were linear over the range of HCQ concentrations tested. It is concluded that HCQ significantly elevated insulin blood concentration resulting in reduced glucose levels in a concentration-dependent fashion in diabetic rats. HCQ may have therapeutic potential in the treatment of type I and type II diabetes.

Animals↗