Triiodothyronine stimulates steroid and VEGF production in murine Leydig cells via cAMP-PKA pathway

Thyroid hormones affect testicular development as well as functions like spermatogenesis and steroidogenesis, thereby influencing male fertility. Our group earlier showed that the stimulatory role of the thyroid hormone, T₃, on the production of vascular endothelial growth factor (VEGF) by murine Leydig cells is mediated by steroids and hypoxia-inducible factor-1 (HIF-1α). The current study further defines the signalling pathway(s) utilised by T₃ to stimulate the production of steroids, VEGF and HIF-1α in mouse Leydig tumour cell line (MLTC-1). Specific inhibitors for different signalling molecules were used to study the role of cyclic AMP (cAMP), and its downstream mediators. Expression of VEGF and HIF-1α mRNA were measured by quantitative RT-PCR; VEGF secretion by ELISA; steroid secretion by radioimmunoassay and HIF-1α protein levels by western blotting. Inhibitors of adenylate cyclase (AC), protein kinase A (PKA), sarcoma kinase (SrcK), phosphoinositide 3-kinase (PI3K) and MAP kinase kinase (MEK1/2) abolished the T₃-induced increase in VEGF mRNA and protein levels. The same signalling molecules also mediated the increased production of steroids and HIF-1α protein in response to T₃. Therefore, it was concluded that T₃ stimulates steroid secretion and HIF-1α protein in MLTC-1 cells through the AC-cAMP-PKA-PI3K-MEK pathway, which in turn stimulate VEGF production.     

Fidaxomicin for the treatment of <Emphasis Type="Italic">Clostridium difficile</Emphasis> infection (CDI) in at-risk patients with inflammatory bowel disease,fulminant CDI,renal impairment or hepatic impairment: a retrospective study of routine clinical use (ANEMONE)

Information is limited or lacking on fidaxomicin treatment of Clostridium difficile infection (CDI) in patients with inflammatory bowel disease, fulminant or life-threatening CDI, severe renal impairment, moderate-to-severe hepatic impairment and pregnancy. The ANEMONE study investigated fidaxomicin use in a routine clinical setting, focusing on these medical conditions of specific interest (MCSIs). This retrospective, post-authorisation study reviewed hospital records from Austria, Germany, Spain and the UK (June 2012–June 2015), collecting data from hospital admission to 30 days after last fidaxomicin dose. The primary objective was to identify the proportion of fidaxomicin-treated patients with MCSIs. Secondary objectives were to describe 30-day mortality, changes in ECG and laboratory parameters, fidaxomicin exposure and CDI response (resolution of diarrhoea; 30-day recurrence). 45.3% (261/576) of patients had ≥?1 MCSI. Thirty-day mortality (post-first dose) was 17.0% (98/576) in the total population and slightly higher (24.6–27.6%) in patients with fulminant CDI or severe renal impairment. 29.6% (24/81) deaths of known cause were attributable to CDI. Of changes in laboratory parameters or ECG findings, only a decrease in leucocyte counts appeared associated with fidaxomicin, consistent with a positive treatment response. Diarrhoea resolved in 78.0% (404/518) of treatment episodes; diarrhoea resolution was lowest in patients with fulminant CDI (investigator-defined, 67.5%, 56/88) and severe renal impairment (68.0%, 68/100). Thirty-day recurrence (18.8%, 79/420) was similar across MCSI subgroups. Although almost half of fidaxomicin-treated patients had ≥?1 MCSI, the majority of patients in all subgroups had positive responses to treatment, and no particular safety concerns were identified.     

The use of a novel tablet application to quantify dysfunction in cervical spondylotic myelopathy patients

Background Context

Despite the prevalence and importance of myelopathy, there is a paucity of objective and quantitative clinical measures. The most commonly used diagnostic tools available are nonquantitative physical exam findings (eg, pathologic reflexes, and gait disturbance) and subjective scoring systems (eg, modified Japanese Orthopaedic Association [mJOA]). A decline in fine motor coordination is a hallmark of early myelopathy, which may be useful for quantitative testing.

Recalcitrant hypertrophic herpes genitalis in HIV‐infected patient successfully treated with topical imiquimod

Herpes Simplex Virus type 2 is the primary cause of genital ulceration worldwide. The presence of atypical features like deep ulcerations, hypertrophic, or pseudotumoural lesions or unusual location can be a marker for co‐infection with HIV. These immunocompromised patients are usually resistant to the conventional antiviral treatment. We present a case of an HIV‐infected patient with hypertrophic herpes genitalis, refractory to conventional oral antiviral therapy, who was successfully treated with a combination of oral valcyclovir and topical application of 5% imiquimod.     

Chemotaxonomic Studies on Centella asiatica (L.) Urb. from Varied Phytogeographical Conditions of India for Its Industrial Prospection

Proceedings of the National Academy of Sciences, India Section B: Biological Sciences - Centella asiatica (L.) Urb. (Apiaceae) with high commercial value is an important herb in traditional Indian...     

Unusual cause of acute mitral regurgitation: idiopathic hypereosinophilic syndrome

Idiopathic hypereosinophilic syndrome (HES) is a rare multisystem condition characterized by dysregulated overproduction of eosinophils. Cardiac involvement in HES is characterized by necrosis from infiltration of eosinophils and thrombus formation and, in the late stage, by fibrosis and chronic valvular regurgitation. We report a very unusual presentation of idiopathic HES with acute mitral regurgitation due to papillary muscle rupture. The transesophageal echocardiogram was suggestive of a flail posterior leaflet and suspicious for endocarditis. Intraoperatively, papillary muscle rupture was seen and the patient underwent mitral valve replacement. The pathologic examination of the valve revealed eosinophilic infiltration of the papillary muscle. The patient was treated with steroids and responded well clinically.     

Draft genome of the red harvester ant Pogonomyrmex barbatus

We report the draft genome sequence of the red harvester ant, Pogonomyrmex barbatus. The genome was sequenced using 454 pyrosequencing, and the current assembly and annotation were completed in less than 1 y. Analyses of conserved gene groups (more than 1,200 manually annotated genes to date) suggest a high-quality assembly and annotation comparable to recently sequenced insect genomes using Sanger sequencing. The red harvester ant is a model for studying reproductive division of labor, phenotypic plasticity, and sociogenomics. Although the genome of P. barbatus is similar to other sequenced hymenopterans (Apis mellifera and Nasonia vitripennis) in GC content and compositional organization, and possesses a complete CpG methylation toolkit, its predicted genomic CpG content differs markedly from the other hymenopterans. Gene networks involved in generating key differences between the queen and worker castes (e.g., wings and ovaries) show signatures of increased methylation and suggest that ants and bees may have independently co-opted the same gene regulatory mechanisms for reproductive division of labor. Gene family expansions (e.g., 344 functional odorant receptors) and pseudogene accumulation in chemoreception and P450 genes compared with A. mellifera and N. vitripennis are consistent with major life-history changes during the adaptive radiation of Pogonomyrmex spp., perhaps in parallel with the development of the North American deserts.     

Intravenous Paracetamol Infusion Versus Intramuscular Tramadol as an Intrapartum Labor Analgesic

Objectives

To compare intravenous paracetamol and intramuscular tramadol as labor analgesics.

Methods

This prospective-randomized study conducted in 200 primigravidae in active labor, distributed into two groups of 100 women each with one receiving intravenous 1,000 mg Paracetamol and other 100 mg intramuscular tramadol. Pain intensity is recorded by McGills scale before, one and 3 h after drug administration. Perinatal outcome is recorded.

Results

No difference in pain intensity is seen before drug administration. After 1 h of drug administration, in paracetamol group, 4 % women had horrible pain, and 29 % had distressing pain, while in tramadol group, 30 % women had horrible pain, and 60 % had distressing pain. After 3 h of drug administration, in paracetamol group, 26 % had distressing pain, while in tramadol group, 51 % women had horrible pain, and 35 % had distressing pain. Labor duration in paracetamol and tramadol group was 4.3 and 5.9 h, respectively. In paracetamol group, nausea is seen in 2.2 % and vomiting in 1.1 %, while in tramadol group, nausea is seen in 6.4 % and vomiting in 4.3 %.

Conclusions

Intravenous paracetamol is more effective labor analgesic with fewer maternal adverse effects and shortens labor as compared to intramuscular tramadol.

     

The relationship of lipid profile and menstrual cycle with acne vulgaris

Objective

The aim of this study was to find lipid profile and hormone levels in patients with severe acne vulgaris and to correlate lipid profile with hormone levels.

Design and methods

Prospective study was performed in the 60 patients of severe acne vulgaris. Lipid profile and serum testosterone, estrogen, and progesterone levels were measured in three consecutive menstrual cycles during luteal phase (19th to 21st day). Their results were compared with a group of 60 age-matched healthy controls.

Results

Total cholesterol (TC), LDL-C, testosterone, and progesterone levels were higher in patients. Estrogen and HDL-C levels were decreased in patients. Positive correlation was found between testosterone and TC and LDL-C. Estrogen levels were positively correlated with VLDL-C, triglyceride levels, and HDL-C and negatively correlated with TC and LDL-C.

Conclusions

These abnormalities must be considered in the pathogenesis of the disease and must be taken into account for the treatment of patients of acne.     

Clinical study of the recurrent flaps of the arm for resurfacing of elbow defects

Defects around the elbow region are often irregular with exposed nerves, tendons, bones/joint, and implants. Skin grafts, though possible in some cases, must be avoided, as it requires prolonged splintage and physiotherapy to prevent recurrence and elbow stiffness. Distant flaps require multiple stages, and free flaps are rarely indicated for elbow defects. Muscle flaps are bulky. To overcome these problems, distally based fasciocutaneous flaps from medial and lateral sides of the arm based on posterior ulnar recurrent artery and radial recurrent artery, respectively, were used. Ten patients were studied. Age of the patients ranged from 10 to 40 years. Five were male, and five were female. Radial and ulnar recurrent flaps were used in five patients each. The largest flap size was 18 × 8 cm, and the smallest was 10 × 6 cm. The flaps were islanded in four cases, and in six cases, they were used as pedicled flaps. Skin grafts were used in 90% of the patients because large flaps were required for resurfacing; also, our patients had thinner arms with less girth. All flaps survived well. One island flap had venous congestion and marginal necrosis, which eventually healed. A significant improvement of mobility and elbow movement was noted in all patients. These flaps can be raised even from the previously burnt skin, as the pedicle is located deep. These flaps have the following advantages: The flap is reliable (deeply located consistent vascular pedicle), can cover both the flexor and extensor surface of the elbow joint, avoids prolonged splintage, elbow stiffness, and recurrence, good aesthetic, and has functional results.