Comparative analysis of biochemical, hormonal, and mineral compositions of preovulatory and cystic ovarian follicles in buffalo during the non-breeding season.

This study is a comparative analysis of the biochemical, hormonal, and mineral compositions of follicular fluid in preovulatory and cystic follicles of water buffalo (Bubalus bubalis). In total, reproductive tracts from 215 buffalo along with intact ovaries were collected randomly from an abattoir. The incidence of cystic conditions found in this study was 3.72% (8/215), involving the right ovary in 62.5% of instances and the left ovary in 37.5% of instances during the non-breeding season. Follicular fluid was aspirated from preovulatory follicles (12-15 mm diameter, oestrogen-active, follicular phase or stage IV corpus luteum on one of the two ovaries, n = 10) and cystic follicles (at least 20 mm diameter, no corpus luteum on any one of the two ovaries, n = 8). The follicular fluid samples were assayed for biochemical components (uric acid, creatinine, blood urea nitrogen, cholesterol, total protein, glucose, ascorbic acid, and alkaline phosphatase), hormones (progesterone, estradiol, and insulin), and minerals (calcium, magnesium, phosphorus, copper, zinc, and cobalt). Cystic follicles had greater (P < 0.05) concentrations of creatinine, blood urea nitrogen, cholesterol, progesterone, copper, zinc, and cobalt, and lesser (P < 0.05) concentrations of uric acid, glucose, ascorbic acid, estradiol, insulin, calcium, magnesium, and phosphorus compared with preovulatory follicles. These results indicated the marked differences in follicular fluid composition between preovulatory and cystic follicles in buffalo. Some of the changes were indicative of oxidative stress and disturbed steroidogenesis, two important mechanisms shown to be associated with cystic ovarian disease in various species. Further studies are warranted to investigate whether these differences are directly or indirectly involved in the formation of cystic follicles or are mere manifestations of the condition.

Slither Into the Heart: Salmonella Endocarditis Following Rattlesnake Meat Ingestion.

Salmonellae foodborne infections are a well described and documented entity, however cardiac complications of Salmonellae foodborne infections including infective endocarditis (IE) are rare. Here we present a case of infective endocarditis as a result of bacteremia caused by multiple species of Salmonella. The patient initially presented with chest pain, fever and altered mental status. Troponin and ECG were unremarkable. The patient was started on empiric antibiotics. Blood cultures grew Salmonella species serotype O&H. Transesophageal echocardiogram (TEE) confirmed aortic valve vegetation. Regional cultural practices suggested possible contamination attributed to ingestion of rattlesnake meat, a practice that has been previously described and well-established in various Hispanic folk practices. Upon further history taking, the patient was found to be regularly consuming dried rattlesnake meat preparations, a rather common practice in Chihuahua desert region. Surgery was not indicated, and the patient was treated with six weeks of antibiotics. This case presents an opportunity to gain insight into such a unique manifestation of Salmonellae, offering a potential facet of information for clinicians to better understand its presentation, susceptibility, and potential adverse outcomes.

Rivaroxaban for Thromboprophylaxis in High-Risk Ambulatory Patients with Cancer.

BACKGROUND: Ambulatory patients receiving systemic cancer therapy are at varying risk for venous thromboembolism. However, the benefit of thromboprophylaxis in these patients is uncertain. METHODS: In this double-blind, randomized trial involving high-risk ambulatory patients with cancer (Khorana score of ≥2, on a scale from 0 to 6, with higher scores indicating a higher risk of venous thromboembolism), we randomly assigned patients without deep-vein thrombosis at screening to receive rivaroxaban (at a dose of 10 mg) or placebo daily for up to 180 days, with screening every 8 weeks. The primary efficacy end point was a composite of objectively confirmed proximal deep-vein thrombosis in a lower limb, pulmonary embolism, symptomatic deep-vein thrombosis in an upper limb or distal deep-vein thrombosis in a lower limb, and death from venous thromboembolism and was assessed up to day 180. In a prespecified supportive analysis involving the same population, the same end point was assessed during the intervention period (first receipt of trial agent to last dose plus 2 days). The primary safety end point was major bleeding. RESULTS: Of 1080 enrolled patients, 49 (4.5%) had thrombosis at screening and did not undergo randomization. Of the 841 patients who underwent randomization, the primary end point occurred in 25 of 420 patients (6.0%) in the rivaroxaban group and in 37 of 421 (8.8%) in the placebo group (hazard ratio, 0.66; 95% confidence interval [CI], 0.40 to 1.09; P = 0.10) in the period up to day 180. In the prespecified intervention-period analysis, the primary end point occurred in 11 patients (2.6%) in the rivaroxaban group and in 27 (6.4%) in the placebo group (hazard ratio, 0.40; 95% CI, 0.20 to 0.80). Major bleeding occurred in 8 of 405 patients (2.0%) in the rivaroxaban group and in 4 of 404 (1.0%) in the placebo group (hazard ratio, 1.96; 95% CI, 0.59 to 6.49). CONCLUSIONS: In high-risk ambulatory patients with cancer, treatment with rivaroxaban did not result in a significantly lower incidence of venous thromboembolism or death due to venous thromboembolism in the 180-day trial period. During the intervention period, rivaroxaban led to a substantially lower incidence of such events, with a low incidence of major bleeding. (Funded by Janssen and others; CASSINI ClinicalTrials.gov number, NCT02555878.).

Endoscope-assisted (with robotic guidance and using a hybrid technique) interhemispheric transcallosal hemispherotomy: a comparative study with open hemispherotomy to evaluate efficacy, complications, and outcome.

OBJECTIVEEndoscope-assisted hemispherotomy (EH) has emerged as a good alternative option for hemispheric pathologies with drug-resistant epilepsy.METHODSThis was a prospective observational study. Parameters measured included primary outcome measures (frequency, severity of seizures) and secondary outcomes (cognition, behavior, and quality of life). Blood loss, operating time, complications, and hospital stay were also taken into account. A comparison was made between the open hemispherotomy (OH) and endoscopic techniques performed by the senior author.RESULTSOf 59 cases (42 males), 27 underwent OH (8 periinsular, the rest vertical) and 32 received EH. The mean age was 8.65 ± 5.41 years (EH: 8.6 ± 5.3 years; OH: 8.6 ± 5.7 years). Seizure frequency per day was 7 ± 5.9 (EH: 7.3 ± 4.6; OH: 15.0 ± 6.2). Duration of disease (years since first episode) was 3.92 ± 1.24 years (EH: 5.2 ± 4.3; OH: 5.8 ± 4.5 years). Number of antiepileptic drugs per patient was 3.9 ± 1.2 (EH: 4.2 ± 1.2; OH: 3.8 ± 0.98). Values for the foregoing variables are expressed as the mean ± SD. Pathologies included the following: postinfarct encephalomalacia in 19 (EH: 11); Rasmussen's syndrome in 14 (EH: 7); hemimegalencephaly in 12 (EH: 7); hemispheric cortical dysplasia in 7 (EH: 4); postencephalitis sequelae in 6 (EH: 2); and Sturge-Weber syndrome in 1 (EH: 1). The mean follow-up was 40.16 ± 17.3 months. Thirty-nine of 49 (79.6%) had favorable outcomes (International League Against Epilepsy class I and II): in EH the total was 19/23 (82.6%) and in OH it was 20/26 (76.9%). There was no difference in the primary outcome between EH and OH (p = 0.15). Significant improvement was seen in the behavioral/quality of life performance, but not in IQ scores in both EH and OH (p < 0.01, no intergroup difference). Blood loss (p = 0.02) and hospital stay (p = 0.049) were less in EH.CONCLUSIONSEH was as effective as the open procedure in terms of primary and secondary outcomes. It also resulted in less blood loss and a shorter postoperative hospital stay.

Hemocompatible curcumin-dextran micelles as pH sensitive pro-drugs for enhanced therapeutic efficacy in cancer cells.

Curcumin, a component in spice turmeric, is renowned to possess anti-cancer therapeutic potential. However, low aqueous solubility and instability of curcumin which subsequently affects its bioavailability pose as major impediments in its translation to clinical application. In this regard, we focused on conjugating hydrophobic curcumin to the hydrophilic backbone of dextran via succinic acid spacer to design a pro-drug. The structural confirmation of the conjugates was carried out using FTIR and (1)H NMR spectroscopy. Critical micelle measurement affirmed the micelle formation of the pro-drug in aqueous media. The size distribution and zeta potential of the curcumin-dextran (Cur-Dex) micelles were determined using dynamic light scattering technique. The micellar architecture bestowed curcumin negligible susceptibility to degradation under physiological conditions along with enhanced aqueous solubility. Biocompatibility of the micelles was proved by the blood component aggregation and plasma protein interaction studies. In vitro release studies demonstrated the pH sensitivity release of curcumin which is conducive to the tumour micro environment. Profound cytotoxic effects of Cur-Dex micelles in C6 glioma cells were observed from MTT and Live/Dead assay experiments. Moreover, enhanced cellular internalization of the Cur-Dex micelles compared to free curcumin in the cancer cells was revealed by fluorescence microscopy. Our study focuses on the feasibility of Cur-Dex micelles to be extrapolated as promising candidates for safe and efficient cancer therapy.

Magnetic and degradable polymer/bioactive glass composite nanoparticles for biomedical applications.

The present study focuses on the development of a biocompatible and biodegradable iron oxide incorporated chitosan-gelatin bioglass composite nanoparticles [Fe-BG]. The developed composite nanoparticle was analyzed by X-ray diffraction (XRD), transmission electron microscopy (TEM), Fourier transform infrared (FTIR) spectroscopy, thermo gravimetric analysis (TG) and differential scanning calorimetry analysis (DSC). The size of the negatively charged composite nanoparticle was in the range of 43-51 nm. The in vitro analysis of the composite nanoparticles was carried out by cell aggregation, protein adsorption and haemolytic activity. The magnetic hysteresis value of the composite nanoparticle showed that it is a soft magnetic material. The presence of iron oxide in the chitosan-gelatin bioglass [BG] matrix enhances biodegradability as indicated in the TG studies. Iron-oxide in equal amount to bioglass in the polymer matrix has been obtained as the optimized system. The developed composite nanoparticle is a soft magnetic material and is suitable for the magnetic hyperthermia treatment and drug delivery. More detailed in vivo studies are needed to confirm the biodegradation profile and biological activity of the material.

A tale of early Reel syndrome caused by an over-enthusiastic masseuse.

Twiddler syndrome is a form of pacemaker lead dislocation caused by the coiling of the pacemaker leads due to pulse generator rotation on its long axis. Similar to Twiddler syndrome, Reel syndrome occurs due to rotation of the pulse generator on its transverse axis, leading to lead dislocation or fracture, followed by clinical symptoms of dislodged leads. We report a case of 75 years old woman with Reel syndrome presenting with syncope.

Neurofibromatosis, pathological fracture and hypervitaminosis-D.

Pathologic fractures in children may be due to various causes. Rarely, it may be the presenting symptom of neurofibromatosis. A misdiagnosis of Rickets and Vitamin D supplementation in such a case may wreak havoc in the form of iatrogenic hypervitaminosis D. We report one such case.

Synthesis and evaluation of lauryl succinyl chitosan particles towards oral insulin delivery and absorption.

In this work a novel chitosan derivative, lauryl succinyl chitosan (LSC) was developed for the purpose of evaluating its applications towards oral peptide delivery system. Nano/microparticles were developed from this derivative by sodium tripolyphosphate (TPP) cross linking. Human insulin was used as the model protein drug and the release kinetics was studied at gastrointestinal pH. The presence of succinyl carboxyl groups had inhibitory effect on the release kinetics of insulin at pH 1.2 minimizing up to about 8.5+/-0.45% in two hours. Results showed that the presence of hydrophobic moieties controlled the release of the loaded insulin from the particles at intestinal pH. The particles were negatively charged with size ranging from 315 nm to 1.090 microm. The mucoadhesive capacity was established ex vivo using the jejunum of rat intestine. Confocal microscopy studies proved the tight junction permeability in Caco 2 cells and in vivo uptake of the FITC-insulin from loaded nanoparticles by the rat intestinal epithelium. The results demonstrated that the modified chitosan with both hydrophilic (succinyl) and hydrophobic (lauryl) moieties had improved the release characteristics, mucoadhesivity as well as the permeability of the insulin compared to the native chitosan particles. The LSC2 particles were capable of reducing blood glucose levels in diabetic rats for the duration of about 6 h. This indicated that this novel derivative could be a promising candidate for oral peptide delivery.

Long-term results of a phase II trial of neoadjuvant chemotherapy followed by esophagectomy for locally advanced esophageal neoplasm.

BACKGROUND: Effective systemic therapy is considered essential to improve the outcome for patients with surgically resectable locally advanced esophageal carcinoma. We report the long-term results of our phase II study of neoadjuvant chemotherapy, followed by esophagectomy and adjuvant chemotherapy for potentially resectable esophageal carcinoma. METHODS: Patients were staged with computed tomography scan (n = 70), endoscopic ultrasonography (n = 63), and laparoscopy with or without thoracoscopy (n = 70). The pretreatment stages were T2N0 (n = 1), T2N1 (n = 15), T3N0 (n = 13), and T3N1 (n = 41). Chemotherapy consisted of 2 or 3 cycles of cisplatin, 5-fluorouracil, and paclitaxel followed by esophagectomy and adjuvant chemotherapy. Patients were monitored for recurrence and survival. RESULTS: A total of 70 patients were enrolled (66 adenocarcinoma, 4 squamous cell carcinoma; 64 men and 6 women; median age, 60 years). Esophagectomy was performed in 63 patients. Operative mortality was 0%. The median overall survival of the entire group was 27.4 months. Seventeen patients were alive at a median follow-up of 62.8 months (range, 39.1 to 142). Fourteen patients were alive without recurrence at a median follow-up of 79 months (range, 39 to 138). Nodal status was an important predictor of overall survival. Patients who were downstaged experienced a significantly improved median survival of 63.4 months versus 21.5 months and overall survival (p = 0.005). CONCLUSIONS: This prospective study for esophageal carcinoma demonstrates encouraging long-term results. In particular, downstaging of the tumor with preoperative chemotherapy is predictive of better long-term outcome. Our results support the role for perioperative chemotherapy for locally advanced resectable esophageal cancer.

Pemetrexed alone or in combination with cisplatin in previously treated malignant pleural mesothelioma: outcomes from a phase IIIB expanded access program.

BACKGROUND: In a randomized phase III trial, pemetrexed plus cisplatin was associated with improved survival compared with cisplatin alone for patients with malignant pleural mesothelioma (MPM). However, there are limited data available on the efficacy of these and other chemotherapy regimens in patients who have received previous systemic chemotherapy. To gather additional efficacy and safety data of pemetrexed/cisplatin and pemetrexed alone in previously treated patients, we examined patients treated on the Eli Lilly and Company expanded access program (EAP). PATIENTS AND METHODS: Patients with malignant mesothelioma were enrolled in this trial. Of 1056 patients receiving at least one dose of the study drug, 187 (17.7%) were previously treated patients with MPM. Patients were treated every 21 days with pemetrexed 500 mg/m alone (n = 91) or in combination with cisplatin 75 mg/m (n = 96) for a maximum of six cycles. All patients received folic acid and vitamin B12 supplementation and steroid prophylaxis. Serious adverse events (SAEs) were reported by investigators and compiled in a pharmaco-vigilance database for all patients enrolled in the EAP. RESULTS: Median age of the previously treated pleural mesothelioma subset was 66 years (range, 27-87 years). Based on 153 evaluable patients (a subset of the larger intent-to-treat population of 187), the overall response rate was 32.5% for pemetrexed and cisplatin and 5.5% for pemetrexed alone. The disease control rate (response rate + stable disease) was 68.7% for pemetrexed and cisplatin and 46.6% for pemetrexed alone. Median survival was 7.6 months for pemetrexed plus cisplatin (67% censored) and 4.1 months for pemetrexed alone (55% censored). The most commonly reported serious adverse events in the overall EAP irrespective of causality were dehydration (7.2%), nausea (5.2%), vomiting (4.9%), dyspnea (3.8%), and pulmonary embolism (2.4%). CONCLUSIONS: The data from this EAP study suggest that patients with previously treated MPM can benefit from treatment with pemetrexed alone or in combination with cisplatin. The treatment is associated with acceptable toxicity.

Genotoxic effects of cadmium chloride and azadirachtin treated singly and in combination in fish.

The genotoxic effects of cadmium chloride (CdCl(2)) and azadirachtin (Aza) were assessed singly and conjointly in a fish, Oreochromis mossambicus, with endpoints such as chromosome aberrations, abnormal red cell nuclei, abnormal sperm morphology, and protein content (both qualitative and quantitative) of selected tissues, namely, muscle, heart, eye, brain, gill, liver, spleen, and kidney. The primary objectives were, first, to examine if CdCl(2), a common pollutant, and Aza, a natural product of the neem plant used extensively as an 'ecofriendly' agent for many purposes, had any genotoxic effect of their own on nontarget aquatic organisms of economic importance; and second, if Aza could have any ameliorating effect on CdCl(2)-induced genotoxicity in O. mossambicus tissues. As compared with distilled water-treated controls, both CdCl(2) and Aza induced genotoxicity in O. mossambicus, the former in greater quantity than that produced by Aza. However, Cd-induced toxicity in O. mossambicus appeared to be ameliorated to some extent by Aza.

Weed control in rose-scented geranium (Pelargonium spp).

Abstract: Field investigations were carried out during 1999 and 2000 to identify effective chemical/ cultural methods of weed control in rose-scented geranium (Pelargonium spp). The treatments comprised pre-emergence applications of oxyfluorfen (0.15, 0.20 and 0.25 kg AI ha(-1)) and pendimethalin (0.50, 0.75 and 1.00kg AI ha(-1)), successive hand weeding, hoeing and mulching using spent of lemon grass (at 5 tonnes ha(-1)) 45 days after planting (DAP), three hand-weedings 30, 60 and 90 DAP, weed-free (frequent manual weeding) and weedy control. Broad-leaf weeds were more predominant than grass and sedge weeds, accounting for 85.8% weed density and 93.0% weed dry weight in 1999 and 77.2% weed density and 93.9% weed dry weight in 2000. Unrestricted weed growth significantly reduced geranium oil yield, by 61.6% and 70.6% in 1999 and 2000, respectively. Pre-emergence application of pendimethalin (0.75-1.00 kgAI ha(-1)) or oxyfluorfen (0.25 kg AI ha(-1)), successive hand-weeding, hoeing and mulching and three hand-weedings were highly effective in reducing weed density and dry weight and gave oil yield comparable to the weed-free check. Application of oxyfluorfen (0.15 or 0.20 kg AI ha(-1)) and pendimethalin (0.50 kg AI ha(-1)) were less effective in controlling the weed species in geranium. None of the herbicides impaired the quality of rose-scented geranium oil measured in terms of citronellol and geraniol content.

Somatization misattributed to non-pathological vaginal discharge.

Lay explanations and attributional patterns about somatization related to vaginal discharge, a folk illness characterized by undue concern about passing (normal) vaginal discharge and believing that their symptoms are caused by this, were surveyed systematically in 200 consecutive women patients with predominant somatic complaints and 138 normal healthy women. Misattribution was reported 3.5 times more often by women with somatic complaints as compared to the normal women. Sixteen women were absolutely certain that their discharge was totally responsible for their symptoms and illness. Thus, somatization related to vaginal discharge seems to be a frequent undetected problem in women with somatic symptoms.

Direct regulation of Na(+)-dependent myo-inositol transport by sugars in retinal pigment epithelium: role of phorbol ester and staurosporin.

An Na(+)-dependent active process for myo-inositol (MI) uptake, sharing a common carrier system with glucose and sensitive to phlorizin, was previously established in primary cultures of bovine retinal pigment epithelial (RPE) cells (26, 32). The present report further examines the nature of glucose-induced inhibition of MI transport in primary cultures of RPE cells. RPE cells were grown in supplemented Dulbecco's modification of Eagle's medium (DMEM) containing 5 mM D-glucose (basic growth media) or 40 mM D-glucose or its nonmetabolizable analogue, alpha-methyl-D-glucoside (alpha MG); 1-5 mM nonradioactive MI, pyruvate, or lactate; or 0.2-20 microM phorbol 12-myristate 13-acetate (TPA) or straurosporin (modified growth media), for up to 4 weeks. The capacity of RPE cells to accumulate 3H-MI (ratios of intracellular transported radioactive MI, [MI]i, to external free MI concentration, [MI]i/[MI]o) decreased by up to 41% or 34% when cells were grown for 10 days or longer with 40 mM D-glucose or 40 mM alpha MG, respectively, compared to cells grown in basic growth media. The rate of uptake of 3H-MI also was reduced to 63 +/- 15% or 48 +/- 8% of the control values when cells were fed 1 or 5 mM nonradioactive MI, respectively. In addition, cellular capacity to bind to [3H]phlorizin was reduced to 52 +/- 7%, 61 +/- 5%, or 38 +/- 6% of the controls when RPE cells were fed 40 mM D-glucose, 40 mM alpha MG, or 5 mM nonradioactive MI, respectively. Growth media containing either pyruvate or lactate, the glucose metabolites, did not suppress the ability of RPE cells to accumulate MI. An 18 +/- 8% reduction in [3H]thymidine incorporation into DNA occurred when cells were grown in 40 mM glucose for 12-14 days, compared to cells grown with 5 mM glucose. Chronic treatment (12-14 days) of the cells with phorbol ester, an activator of protein kinase C, caused up to twofold increase in MI uptake, [3H]phlorizin binding, cell number, and DNA synthesis. However, when the rates of MI uptake into cells grown in basic growth media or TPA-treated media were normalized to cell number, no significant difference in MI uptake was found between the treated and untreated cells. Addition of staurosporin, a protein kinase C inhibitor, together with TPA, in the growth media reversed the phorbol-induced increase of MI uptake.(ABSTRACT TRUNCATED AT 400 WORDS)

A host-mediated in vivo/in vitro assay with peritoneal murine macrophages for the detection of carcinogenic chemicals.

We have developed a host-mediated assay system for the detection of the transforming action of chemical carcinogens on peritoneal macrophages. Directly as well as indirectly acting carcinogenic substances administered intraperitoneally to NMRI mice could be examined in this way. Resident macrophages were recovered by peritoneal lavage from treated and untreated mice and were cultured in soft agar. After 5-6 days normal and transformed cells could be distinguished. Statistical analysis comparing cells, for example, from alpha-naphthylamine or diphenylhydantoin-treated animals with those from control mice proved that the test is positive at least on a significance level of 5% using the t-test. Further substances revealing a cell-transformation potential were benzene, benz(a)pyrene, 2,3,7,8-tetrachlorodibenzodioxin, N-nitrosodimethylamine, ethidium bromide, aflatoxin B1,N-methyl-N-nitrosourea, 1-methyl-3-nitro-1-nitrosoguanidine, 2-naphthylamine, dieldrin, suramin and trichloroethylene. A weak transforming potential was found for chlorambucil as well as for tetrachloroethylene. With toluene or azidothymidine no cell transformation could be observed. Several immortal cell lines could be established form NMRI mice treated with alpha-naphthylamine or N-methyl-N-nitrosourea. Athymic nu/nu mice injected subcutaneously with these cells developed tumors, establishing the oncogenic potential of these cell lines.

Cellular kinetics in a patient with Sezary syndrome.

Cellular kinetics and proliferation of Sezary cells (SC) were studied in a 48-year-old woman with Sezary syndrome (SS). In vitro flash labeling indices of peripheral blood (PB) SC were studied by labeling with tritiated thymidine (3HTdR) and tritiated cytidine (3HCdR). Intradermal SC were labeled in vivo by local injection of 3HTdR followed by skin biopsies of the injected sites. Traffic patterns of DNA labeled PB SC were studied by intravenous 3HTdR followed by sampling of PB, skin, lymph node (LN), and bone marrow (BM). Fluxes of PB SC in various tissues were investigated by autotransfusion of 3HCdR labeled PB SC followed by serial sampling of PB, LN, BM, and skin. In vitro response of PB SC followed by serial sampling of PB, LN, BM, and skin. In vitro response of PB SC to phytohemagglutinin (PHA), concanavalin A (Con A), and pokeweed (PWM) were also investigated. The results from these studies in this patient indicate that 1) proliferation of SC was primarily in the skin, 2) there was a negligible flux of SC from blood into skin, LN, and BM, and 3) the mitogenic response of PB mononuclear cells (mostly SC) to PHA, PWM, and Con A was poor.