Comparison of efficacy, safety and brain derived neurotrophic factor (BDNF) levels in patients of major depressive disorder, treated with fluoxetine and desvenlafaxine.

This randomized, open label, prospective, observational study compared clinical efficacy, safety alongwith plasma BDNF levels in outpatients of depression treated with fluoxetine and desvenlafaxine. Patients (aged 18-60 years) with moderate to severe major depressive disorder (MDD) diagnosed by DSM-IV criteria, and Hamilton Rating Scale for Depression (HAM-D) score ≥14, who were prescribed fluoxetine or desvenlafaxine were included (n=30 in each group). Patients were followed up for 12 weeks for evaluation of clinical efficacy, safety along with BDNF levels. In the fluoxetine group, HAM-D scores at the start of treatment was 19±4.09 which significantly (p<0.05) reduced to 9.24±3.98 at 12 weeks. In the desvenlafaxine group, HAM-D scores at the start of treatment was 18±3.75 which significantly (p<0.05) reduced to 10±3.75 at 12 weeks. The BDNF levels in the fluoxetine group were 775.32±30.38pg/ml at the start of treatment which significantly (p<0.05) increased to 850.3±24.92pg/ml at 12 weeks. The BDNF levels in the desvenlafaxine group were 760.5±28.53pg/ml at the start of treatment which significantly (p<0.05) increased to 845.8±32.82pg/ml at 12 weeks. Both the antidepressants were found to be safe and well tolerated. The efficacy and the safety profile of desvenlafaxine is comparable to fluoxetine in patients of MDD. BDNF levels were significantly increased post-treatment with both the antidepressive agents. Whether BDNF may have a prognostic value in predicting treatment response to antidepressant drugs needs to be investigated in a larger patient population.

Comparison of aqueous humour concentration after single high dose versus multiple administration of topical moxifloxacin in rabbits.

For the prevention of postoperative ocular infections prophylactic topical antibiotics are routinely used. Studies evaluating comparative difference between single dose versus multiple dose administration on aqueous humour concentration of moxifloxacin are lacking. This study compared the aqueous humour concentration of moxifloxacin following its topical administration in rabbit eyes with two dose regimens. Twelve albino rabbits were divided into two groups. In group-1, two drops were administered thrice (total six drops) at 2 min intervals, in both the eyes; in group-2, two drops of moxifloxacin were administered three times a day for three days and also two h before aqueous humour collection i.e. on fourth day. Mean aqueous humour concentrations were calculated and compared using Student's 't' test and P<0.05 was considered significant. Moxifloxacin concentration in aqueous humour in group-1 was 23.79 µg/ml and in group-2 was 42.08 µg/ml. Both dosing regimens produced substantially higher aqueous concentrations than the known minimum inhibitory concentration for most bacteria. Moxifloxacin concentration in aqueous humour with multiple instillations is significantly higher than single instillation (P<0.05), which is adequate to cover ciprofloxacin-resistant gram-negative bacteria. Repeated topical moxifloxacin administration achieved significantly higher aqueous humour concentrations than single administration.

Naloxone blocks the beneficial effects of aqueous extract of Murraya koenigii (L.) Spreng leaves in models of pain.

AIM: This study investigated the antinociceptive effects of aqueous extract of Murraya koenigii (AEMK) leaves (200, 400 and 800 mg/kg, orally) on animal models of acute and persistent pain and its modulation by naloxone. MATERIALS AND METHODS: Antinociceptive effects were assessed using tail-flick, hot plate and formalin tests in mice. To differentiate between central and peripheral antinociceptive effect of AEMK, naloxone (2 mg/kg) was administered along with the 800 mg/kg dose of extract. Morphine was used as a standard drug. RESULTS: AEMK and morphine significantly increased the tail-flick latency (tfl) and paw licking/jumping latency in tail-flick and hot plate tests, respectively, in comparison to control. Also, in both the tests AEMK and morphine significantly increased the AUC0-120 min. In formalin test, AEMK (400 mg/kg and 800 mg/kg) and morphine significantly reduced licking time in both early and late phases in comparison to control. CONCLUSIONS: Thus, in all three pain models AEMK showed antinociceptive effect, which was blocked by naloxone suggesting the involvement of opioidergic central mechanism.

N-Methyl-D-aspartate receptor modulators block hyperalgesia induced by acute low-dose morphine.

1. Following opioid-induced antinociception in mice, hyperalgesic responses may be observed. The present study was designed to evaluate the effect of different N-methyl-d-aspartate (NMDA) receptor modulators (magnesium, dextromethorphan, d-serine) on the development of morphine-induced hyperalgesia in mice. The tail-flick test was used to assess the effects of morphine alone and in combination with the NMDA receptor modulators. 2. Administration of a single low dose (2 mg/kg) of morphine to mice produced antinociception that was followed by hyperalgesia. 3. Administration of magnesium sulphate (5 mg/kg) and d-serine (10 mg/kg) alone produced a transient antinociceptive response, whereas dextromethorphan (10 mg/kg) alone produced a prolonged antinociceptive response that had a relatively delayed onset after 4 h. 4. When coadministered with morphine, the NMDA receptor blockers magnesium (2 mg/kg) and dextromethorphan (2 and 5 mg/kg) and the NMDA receptor agonist d-serine (2, 5 and 10 mg/kg), maintained the duration of the antinociceptive response to morphine and inhibited the development of the hyperalgesic response. Coadministration of dextromethorphan (10 mg/kg) with morphine produced antinociception at 30-120 min and at 4-24 h. 5. The results of the present study suggest that coadministration of low-dose NMDA receptor antagonists, as well as the NMDA receptor agonist d-serine, with morphine can inhibit morphine-induced hyperalgesia.

Potency of mephentermine for prevention of post-spinal hypotension.

This study was designed to determine the minimum effective dose (ED50) of mephentermine for prevention of post-spinal hypotension in women undergoing elective caesarean section. Dixon's up-down method of sequential allocation was used to determine the patient's dose of vasopressor drug. In our previous study, mephentermine appeared to be much more potent than ephedrine, so the present study was conducted using a lower initial dose and smaller dose interval for this vasopressor. Following administration of spinal anaesthesia, a prophylactic infusion of mephentermine was started with 5 mg infused over a period of 30 minutes as the initial dose and a dose interval of 1 mg. The ED50 of mephentermine of 3.7 mg (95% confidence interval 2.4 to 5.7 mg) was much less than that of ephedrine, as calculated in our previous study using the same methodology. Using these values gives a potency ratio of ephedrine to mephentermine of 1:6.8 (95% confidence interval 6.0 to 7.5).

Comparison of potency of ephedrine and mephentermine for prevention of post-spinal hypotension in caesarean section.

The dosages and potency of intravenous mephentermine for prevention of post-spinal hypotension are not available in English literature. This study was designed to determine the minimum effective dose (ED50) of mephentermine and to compare its potency with that of ephedrine for prevention of post-spinal hypotension in parturients undergoing caesarean section. Dixon's up-down method of sequential allocation was used for vasopressor doses. Following administration of spinal anaesthesia, patients received a prophylactic infusion with 50 mg infused over a period of 30 minutes as the initial dose and dose intervals of 5 mg, of either ephedrine or mephentermine. The ED50 of ephedrine was 25.0 mg (95% CI 15.5 to 40.4 mg). For mephentermine, the up-down method was abandoned due to the success of the minimum dose possible but the ED50 appeared to be less than 5 mg. In conclusion, the minimum effective dose of mephentermine is much less than that of ephedrine for prevention of post-spinal hypotension. Another trial with a lower starting dose and smaller dose interval of mephentermine is required to determine the potency ratio of mephentermine and ephedrine.

Cell adherence--a determinant of virulence in Yersinia enterocolitica.

The adherence of pathogenic bacteria to eukaryotic cells plays a central role in their ability to colonize the mucosal epithelial surfaces. The adherence by Y. enterocolitica to the mucosal surface of the gut is the initiating event leading to penetration of mucosa. Adhesion of 10 probable pathogenic and one non-pathogenic isolate was studied using ileum and colon epithelial cells of mouse for 90 minutes. Adhesion study revealed that isolates of Y. enterocolitica had a good adhesive property while non pathogenic showed negligible adherence. All isolates showed better adherence to colon epithelial cells. The organism continued to be excreted in faeces up to 8-10 days after oral feeding. Adhesion positive isolates were found to be virulent when tested in mice for diarrhoea and death. Adhesion was found to be thermoregulated.

Juvenile hyaline fibromatosis in siblings.

Juvenile hyaline fibromatosis (JHF) is a rare, autosomal recessively inherited disorder. We report two siblings with multiple large tumors on the scalp, translucent papules on the nape of the neck, hypertrophic gingiva, and severe flexural contractures of large joints. The histopathology from the skin lesions showed features characteristic of juvenile hyaline fibromatosis. The cases are being reported on account of the extreme rarity of the condition.

Florid cutaneous papillomatosis with adenocarcinoma of stomach in a 35 year old male.

Various paraneoplastic dermatoses may be seen in association with underlying visceral, especially gastrointestinal, malignancy. Florid cutaneous papillomatosis describes the sudden appearance of multiple acuminate keratotic papules that morphologically resemble viral warts. It may be seen in association with acanthosis nigricans and/or the sign of Leser Triotalat. We report a 35-year-old male with extensive seborrhoeic keratoses and florid cutaneous papillomatosis. Unusually marked verrucous changes caused disfigurement of the hands and feet. The patient also reported dyspepsia, abdominal distention and weight loss 6 months prior to the development of cutaneous lesions. Gastroscopy revealed a large growth in the stomach. Histopathology of the tumor showed features of adenocarcinoma.

Occupational contact dermatitis among the traditional 'tie and dye' cottage industry in Western Rajasthan.

BACKGROUND: Dyeing is an age-old process and forms an integral part of textile industries. Tying is a process by which a particular part of cloth is prevented from the process of dyeing. The skin diseases in workers engaged in the 'tie and dye' industry have not been extensively studied. AIMS: To study the prevalence of contact dermatitis among workers engaged in the 'tie and dye' industries in and around Jodhpur (Western Rajasthan). METHODS: One thousand three hundred workers engaged in 'tie and dye' work were evaluated for occupation-related dermatitis. Those with skin lesions were subjected to patch tests using 2% aqueous solution of the dyes and chemicals commonly used by them. These included direct dyes, VAT dyes, sulfur dyes and azo dyes. Fifty workers without skin lesions served as controls. RESULTS: One hundred patients (7.69%) had dermatitis involving the exposed sites, mainly the hands and forearms. Eighty-one patients showed positive reactions to one or more dyes, most commonly Red RC base (azo dye), followed by naphthol. CONCLUSION: Red RC base and naphthol were the commonest allergens in the 'tie and dye' industry.

Histopathological and ultrastructural alterations of induced Yersinia enterocolitica infection in mice.

Yersinia enterocolitica is an enteric bacterium and infections by this organism are mostly foodborne. It has been implicated to cause enterocolitis, terminal ilitis. diarrhoea, mesenteric lymphadenitis and arthritis in man. Due to paucity of information regarding histopathological and specially ultrastructural alterations in tissues affected, this study was planned with mice as the experimental model. Nine pathogenic Y.enterocoliticaisolates were used to infect 80 albino mice by oral and intraperitoneal route. Pathological alterations were studied by light and electron microscopy. Histopathological examination of intestines showed severe edema, purulent enteritis, goblet cell hyperplasia infiltration of mononuclear cells, thickening of mucosa and necrosis of the tips of villi. Liver showed congestion, hepatocellular degeneration and necrosis, atrophy of hepatocytes and microabcesses. The lungs revealed congestion, edema, haemorrhage and purulent ronchopneumonia, while kidneys showed mild necrotic changes and bacterial emboli in glomeruli. Ultrastructural changes were indicative of mitochondrial degeneration and their loss in kidneys, membranous degeneration with formation of myelin figures in lungs and disorganization, disruption and bleb formation of microvilli in intestines. Y.enterocolitica caused significant histopathological and ultrastructural alterations in experimentally infected mice. Variation in pathogenicity of different strains of Y.enterocolitica was also observed.

Y. enterocolitica gastroenteritis - a prospective study.

Two thousand faecal samples were collected from diarrhoeal patients of all age groups and processed by using MacConkey agar and Yersinia selective agar [Cefsulodin-Irgasan-Novobiocin (CIN) media]. One hundred and seventy faecal samples from non-diarrhoeal (healthy controls) were also processed. Samples were subjected to cold enrichment before processing. Three hundred and seventy-four (18.7%) faecal samples were positive for bacterial pathogens, of which 41 (2.05%) had Y. enterocolitica infection. Y. enterocolitica was more common in patients above 16 years of age 23/41 (56%). Higher rates of isolation were recorded during winter months. Of the typable isolates 21.9% belonged to 0:3 serotype followed by 01, 2a, 3 (17%) serotype. Twelve (29.2%) isolates were untypable. 51.2% isolates of Y. enterocolitica belonged to biotype IV whereas 24.4%, 19.5%, 4.9% belonged to type I, II and III respectively. Majority of the isolates were found sensitive to chloramphenicol, gentamicin, amikacin, ciprofloxacin, ampicillin, netromycin, cefoperazone, tobramycin and pefloxacin. All isolates were resistant to ofloxacin.