Hepatic effects of repeated oral administration of diclofenac to hepatic cytochrome P450 reductase null (HRN™) and wild-type mice

Hepatic NADPH-cytochrome P450 oxidoreductase null (HRN?) mice exhibit normal hepatic and extrahepatic biotransformation enzyme activities when compared to wild-type (WT) mice, but express no functional hepatic cytochrome P450 activities. When incubated in vitro with [¹⁴C]-diclofenac, liver microsomes from WT mice exhibited extensive biotransformation to oxidative and glucuronide metabolites and covalent binding to proteins was also observed. In contrast, whereas glucuronide conjugates and a quinone-imine metabolite were formed when [¹⁴C]-diclofenac was incubated with HRN? mouse liver, only small quantities of P450-derived oxidative metabolites were produced in these samples and covalent binding to proteins was not observed. Livers from vehicle-treated HRN? mice exhibited enhanced lipid accumulation, bile duct proliferation, hepatocellular degeneration and necrosis and inflammatory cell infiltration, which were not present in livers from WT mice. Elevated liver-derived alanine aminotransferase, glutamate dehydrogenase and alkaline phosphatase activities were also observed in plasma from HRN? mice. When treated orally with diclofenac for 7 days, at 30 mg/kg/day, the severities of the abnormal liver histopathology and plasma liver enzyme findings in HRN? mice were reduced markedly. Oral diclofenac administration did not alter the liver histopathology or elevate plasma enzyme activities of WT mice. These findings indicate that HRN? mice are valuable for exploration of the role played by hepatic P450s in drug biotransformation, but poorly suited to investigations of drug-induced liver toxicity. Nevertheless, studies in HRN? mice could provide novel insights into the role played by inflammation in liver injury and may aid the evaluation of new strategies for its treatment.     

Variation in the insertion of the palmaris longus tendon

The palmaris longus is harvested as a tendon graft in various surgical procedures. We herein report the variations in the insertion of the palmaris longus tendon. During a routine dissection, a rare variation in the insertion of the palmaris longus tendon was observed. In the left forearm, the palmaris longus tendon bifurcated, while in the right forearm, the palmaris longus tendon trifurcated, giving rise to an accessory muscle, which passed superficial to the ulnar artery and ulnar nerve. The accessory muscle was supplied by a deep branch of the ulnar nerve, and the ulnar artery was observed to be tortuous. During reconstructive surgeries, surgeons should bear in mind the accessory muscle. Also, since the palmaris longus muscle provides a very useful graft in tendon surgery, every surgeon should be aware of the variations in the insertion of the palmaris longus tendon.     

Sharma's parachute sign a new laparoscopic sign in abdomino pelvic tuberculosis

AimsTo demonstrate a new laparoscopic sign “Sharma's Parachute sign” in abdominopelvic tuberculosis in women with infertility.MethodsA total of 104 women who were diagnosed to have abdominopelvic tuberculosis, on endometrial sampling or on laparoscopy were enrolled in this ongoing study on tuberculosis in infertility. A new laparoscopic “Sharma's parachute sign” was looked for in these cases on laparoscopy.ResultsThe mean age, pairty and duration of infertility was 27.6 years, 0.58 and 4.1 years respectively. Menstrual dysfuction were common especially hypomenorrhoea (34.61%), oligomenorrhoea (36.53%) along with constitutional symptoms and abdomino pelvic pain or lump. Diagnosis of abdominopelvic tuberculosis was made by identification of acid fast bacilli (AFB) on microscopy or culture of endometrial aspirate or peritoneal biopsy or positive gene Xpert or positive polymerase chain reaction (PCR) or histopathological demonstration of epithelioid granuloma on endometrial or peritoneal biopsy, various laparoscopic findings on pelvic and abdominal organs were tubercles and shaggy areas (white deposits, caseous nodules encysted ascites, abdominal and pelvic adhesions, tubal findings (hydrosalpinx, pyosalpinx, beaded or calcified tubes). A new “Sharma's parachute sign”in which ascending colon was totally adherent to anterior abdominal wall with its mesocolon looking like an open parachute with small caseous nodule was seen in 11 (10.5%) cases.ConclusionDiagnostic laparoscopy is an important investigation for abdominopelvic tuberculosis showing various adhesions including new parachute sign.     

Dry mouth: saliva substitutes which adsorb and modify existing salivary condition films improve oral lubrication

Clinical Oral Investigations - The aims of this study are to assess different saliva substitutes for their efficacy to lubricate the oral cavity, and to relate this oral lubrication to the ability...     

Stress Testing Versus CT Angiography in Patients With Diabetes and Suspected Coronary Artery Disease

Background

The optimal noninvasive test (NIT) for patients with diabetes and stable symptoms of coronary artery disease (CAD) is unknown.

Effect of lacosamide on ethanol induced conditioned place preference and withdrawal associated behavior in mice: Possible contribution of hippocampal CRMP-2

BackgroundExcessive consumption of ethanol is known to activate the mTORC1 pathway and to enhance the Collapsin Response Mediator Protein-2 (CRMP-2) levels in the limbic region of brain. The latter helps in forming microtubule assembly that is linked to drug taking or addiction-like behavior in rodents. Therefore, in this study, we investigated the effect of lacosamide, an antiepileptic drug and a known CRMP-2 inhibitor, which binds to CRMP-2 and inhibits the formation of microtubule assembly, on ethanol-induced conditioned place preference (CPP) in mice.MethodsThe behavior of mice following ethanol addiction and withdrawal was assessed by performing different behavioral paradigms. Mice underwent ethanol-induced CPP training with alternate dose of ethanol (2 g/kg, po) and saline (10 ml/kg, po). The effect of lacosamide on the expression of ethanol-induced CPP and on ethanol withdrawal associated anxiety and depression-like behavior was evaluated. The effect of drug on locomotor activity was also assessed and hippocampal CRMP-2 levels were measured.ResultsEthanol-induced CPP was associated with enhanced CRMP-2 levels in the hippocampus. Lacosamide significantly reduced the expression of ethanol-induced CPP and alleviated the levels of hippocampal CRMP-2 but aggravated withdrawal-associated anxiety and depression in mice.ConclusionThe present study demonstrated the beneficial effect of lacosamide in attenuation of expression of ethanol induced conditioned place preference via reduction of hippocampal CRMP-2 level. These findings suggest that lacosamide may be investigated further for ethanol addiction but not for managing withdrawal.