OBJECTIVE: The objective of the study was to characterize the mechanism associated with metabolic syndrome (MetS)-associated cognitive decline and determine the effect of minocycline on the above condition in mice. MATERIALs AND METHODS: We developed a HFHC diet-induced MetS model in mice. Diagnostic characteristics of MetS including waist circumference, lipid levels, blood pressure, and fasting blood glucose were measured in these Swiss albino mice. Cognitive parameters were measured using passive avoidance and elevated plus maze test. Hippocampal acetylcholine esterase (AchE), reduced glutathione (GSH), and cytokine levels were measured and histopathological evaluation conducted. The MetS animals were administered minocycline (50 mg/kg; 10 days) and the above parameters were measured. RESULTS: We successfully induced MetS using HFHC diet in mice. Animals showed significantly higher fasting blood glucose levels (P < 0.001), systolic blood pressure (P < 0.01), waist circumference (P < 0.001), low-density lipoprotein (P < 0.001), and triglyceride (P < 0.01) and reduced high density lipoprotein levels (P < 0.05) compared to control animals. Both scopolamine and MetS significantly lowered (P < 0.01) step-down latency and increased transfer latency (P < 0.001). MetS animals showed significantly higher AchE (P < 0.001) and tumor necrosis factor-α (P < 0.001) and Interleukin-1 β (P < 0.01) and lower GSH (P < 0.001) levels and reduced both CA1 (P < 0.001) and CA3 (P < 0.01) neuronal density compared to controls. Minocycline treatment partially reversed the above neurobehavioral and biochemical changes and improved hippocampal neuronal density in MetS animals. CONCLUSION: MetS led to hippocampal oxidative stress and neuroinflammatory changes with a corresponding loss of hippocampal neuronal density and cognitive decline. Anti-inflammatory and antioxidant property of minocycline may be responsible for its neuroprotective actions in these animals.

OBJECTIVES: Urinary tract infection (UTI) is a frequent disorder and depends on age and gender. Ineffective empiric treatment of UTI is common when associated with extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae. The aim of the study was to investigate the prevalence of Gram-negative uropathogens of E. coli and K. pneumoniae in different age groups along with the identification of ESBL-producing uropathogens and antimicrobial susceptibility profiles. MATERIALS AND METHODS: A total of 247 uropathogens of E. coli and K. pneumoniae were collected over a period of 1 year (January–December 2015) from various diagnostic centers of Karachi city (Pakistan). Antimicrobial susceptibility analysis was performed by disc diffusion method, and identification of ESBL was performed by double disc synergy test. Categorical data of ESBL and non-ESBL uropathogens were analyzed by Pearson's Chi-square test. RESULTS: The study of 247 patients with community-acquired UTI comprised 72% females and 28% males, illustrating an increased prevalence of UTIs among females. It was also revealed that 90% belonged to the age group of 16–30 years whereas 78% related to the age group of 46–60 years. ESBL was found positive in 33.5% (63/188) of E. coli and 15.25% (9/59) in K. pneumonia, with a significant association i.e., (p=0.007). Amikacin, fosfomycin, imipenem, and tazobactam/piperacillin were found to be the effective treatment options. A significant association was found between ESBL-producing uropathogens against ciprofloxacin, enoxacin, and amoxicillin/clavulanic acid resistance (P < 0.05). CONCLUSIONS: It was concluded that for effective treatment of UTIs, appropriate screening of ESBL and culture sensitivity must be employed instead of empiric treatment.

OBJECTIVES: In our preliminary study, chromium malate could decrease the blood glucose level in mice with diabetes and exhibits good benefits in treating glycometabolism and adipose metabolization obstacle in rats with type 2 diabetes. This study was aimed at assessing the pharmacokinetics and bioavailability of chromium malate and influence on trace metals absorption in rats. METHODS: BAPP 2.3 pharmacokinetic calculating program (China Pharmaceutical University Medicine Center) was used to calculate the pharmacokinetic parameters. Models of type 2 diabetic mellitus rats were applied to analyzed Ca, Mg, Fe, Cu, and Zn contents. RESULTS: The results showed that mean retention time (MRT) in chromium malate group was significantly prolonged and the area under the curve (AUC) and relative bioavailability of chromium malate (male) group were significant increase compared to chromium picolinate group. The serum Ca, Mg, Fe, Cu, and Zn contents in chromium malate (at doses of 15 and 20 μg Cr/kg bw) groups were significantly increased compared to control group, chromium trichloride group, and chromium picolinate group in type 2 diabetes mellitus rats. CONCLUSIONS: Those results indicated that chromium malate can significantly prolong MRT and increase AUC (male). Moreover, chromium malate is more effective at treating increased serum Ca, Mg, Fe, Cu, and Zn contents compared to chromium trichloride and chromium picolinate.

OBJECTIVES: Dimethyl sulfoxide (DMSO) is commonly used as a vehicle for many hydrophobic drugs. This study aimed at evaluating the effect of low dose of DMSO (0.1%) on Pentylenetetrazole(PTZ) induced neuronal damage in rats. MATERIALS AND METHODS: Young male Wistar rats (n = 32) were divided into four groups as follows: saline control group, DMSO control group, PTZ group (35 mg/kg), and combination group (DMSO + PTZ). Animals were observed for seizure score, latency to develop kindling, percentage of animals kindled, and histopathological score of hippocampus. RESULTS: There was a significant increase in the seizure scores and histopathological scores in the combination group as compared to PTZ-treated group. The latency to develop kindling was, however, decreased in the combination group (4th week) as compared to PTZ (6th week) group. CONCLUSIONS: The present study has concluded that 0.1% DMSO in PTZ-induced rat model of epileptogenesis needs further optimization and should be used cautiously

Agranulocytosis is a rare documented side effect of clozapine which can be associated with grave consequences. When it is associated with other blood dyscrasia, prognosis worsens further. In literature, there are very few cases of pancytopenia and bicytopenia caused by clozapine. We present a case of bicytopenia (reduced white and red blood cells' counts) caused by clozapine within a month of therapy and complicated by a Klebsiella pneumoniae infection. Patient improved in 3 weeks after stopping clozapine along with medical management in the Intensive Care Unit. Such side effects, though rare, can be life threatening and warrants intermittent complete blood monitoring besides regular assessment of granulocytes and neutrophils when any patient is prescribed clozapine.

Angina bullosa hemorrhagica (ABH) is an infrequent dermatosis characterized by acute onset of hemorrhagic bulla in the oral cavity. Clinical presentation of ABH may be quite worrisome, and clinicians often feel skeptical regarding their clinical diagnosis and lack confidence in managing this distinct entity. Indeed, ABH is a completely benign and self-limited disorder. The exact etiopathogenesis of ABH is still unknown. There have been reports in the literature addressing a central role for mechanical instability of the epithelial-connective tissue connection in the pathogenesis of ABH. Moreover, it has been claimed that long-term usage of inhaled glucocorticoids (GCs) is involved in the development of ABH, since most of the reported cases are asthmatic patients, who were treated with inhaled GCs, and GCs are well known for their degradative activities on collagen formation. Here, we describe a case with ABH, who had a drug history of inhaled GCs and nonsteroidal anti-inflammatory drugs (NSAIDs). We assume that our case not only supports the association of inhaled GCs with ABH but also suggests a possible role for NSAIDs in the pathogenesis of ABH.

Cyclosporine is one of the main drugs used for the prophylaxis of graft versus host disease in bone marrow transplanted patients. Hypersensitivity reaction to intravenous cyclosporine is rare and might be due to its vehicle polyoxyethylated castor oil, Cremophor EL. The exact mechanism is unknown, but IgE and IgG antibodies, complement, and histamine release have been considered to play a role in the development of this reaction. Here, we describe a case of anaphylaxis to intravenous cyclosporine, which was developed in a 19-year-old Iranian female with acute myeloid leukemia who underwent allogeneic bone marrow transplantation from her sister. The corn oil-based soft gelatin capsule (Sandimmune^®) was substituted with no reaction. Our observation along with the previous reports confirms the role of Cremophor EL in hypersensitivity reaction to cyclosporine, according to which, modifying the formulation of the intravenous (IV) form could be the solution for this problem.