Developmental regulation of type 1 and type 3 interferon production and risk for infant infections and asthma development

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The 3' end of hepatitis E virus (HEV) genome binds specifically to the viral RNA-dependent RNA polymerase (RdRp)

Hepatitis E virus (HEV) is the major cause of acute epidemic and sporadic hepatitis in the developing world. It is a positive-strand RNA virus with a genome length of about 7.2 kb. The replication mechanism of this virus is virtually unexplored. Identification of the regulatory elements involved in initiation of replication may help in designing specific inhibitors for therapy. In the positive-stranded RNA viruses the initiation of replication requires interaction of the 3' end of genome with its RNA-dependent RNA polymerase (RdRp) and possibly host-derived cofactors for synthesis of the minus-strand replicative intermediate. Secondary structure prediction of the conserved 3' end of the infectious HEV genome was carried out to identify possible stem-loop structures necessary for RNA-protein interaction and the model was confirmed by structure probing experiments. Electrophoretic mobility-shift assays showed specific binding of purified and refolded recombinant HEV RdRp protein to the 3' end of its RNA genome containing the poly(A) stretch. Mutations at the 3' end, in which the stem-loop structures were partially or completely destroyed or recreated revealed that the two stem-loop structures SL1 and SL2 at the 3' end and the poly(A) stretch are necessary for this binding. The interacting nucleotides in such an interaction were further identified by generating footprints of the complex by Pb(II)-induced hydrolysis. This specific binding of viral RdRp to the 3' end of HEV RNA directs the synthesis of complementary-strand RNA and thus such a binding domain might assume the role of a possible cis-acting element as a potential site for the initiation of replication.     

Hypothalamic control of thyrotrophin secretion

1. By means of the haemagglutination-inhibition technique, it has been possible to measure the plasma and pituitary levels of thyroid-stimulating hormone (TSH) following unilateral and bilateral electrolytic lesions placed in the supraoptic area of the hypothalamus of female rats.

2. Unilateral lesions after 8 and 48 hr caused a temporary decrease in the percentage of circulating TSH followed by a return to normal.

3. Bilateral lesions caused a fall in plasma TSH to a level 41% below normal at 10 days whereas the pituitary level increased 70%.

4. Rats with bilateral symmetrical supraoptic lesions, kept for 3 days at 4° C, had a lower plasma TSH content (23%) and a higher pituitary TSH content (16%) than the sham operated control animals but the levels of pituitary TSH did not show any significant difference (0·100 > P > 0·050).

5. Thyroidectomized rats with bilateral lesions kept at 26° C for 3 days had a much lower plasma TSH (39%) and a slightly higher pituitary TSH as compared to the normal intact animals, suggesting that the hypothalamus also influences the synthesis of TSH in the pituitary.

6. Thyroidectomized rats with bilateral lesions kept at 4° C for 3 days showed both a plasma and pituitary TSH increase compared to controls at 26° C, suggesting that when a higher demand for thyroid function is present the pituitary gland has some autonomy for both secretion and release of TSH. This autonomy appears to be slight, as there was no statistically significant difference between the pituitary TSH levels of the thyroidectomized animals bearing similar supraoptic lesions and exposed to 4 and 26° C.

     

Effect of verapamil on the non-adrenergic response of the field stimulated rat vas deferens

A comparison has been made, in the present study, between the effects of verapamil (reported to have smooth muscle depolarizing action) and K+ depolarization on the responses of noradrenaline, ATP and those of field stimulation on the vas deferens obtained from reserpinized rats. Field stimulation of the vas using single pulse (1 ms pulse width; supramaximal voltage) resulted in a fast twitch response reaching a maximum at 300 +/- 20 ms. Verapamil (6 X 10(-6) M) significantly potentiated this response. Verapamil potentiated the twitch component of the biphasic response resulting from field stimulation of the intrinsic nerves with repetitive pulses, while the tonic component was markedly inhibited. Verapamil enhanced the ATP (7 X 10(-5) M) response, while the phasic and tonic components of KCl (5.36 X 10(-2) M)-induced biphasic responses were nearly abolished. While the phasic component of the noradrenaline (7 X 10(-6) M) response remained unaltered in the presence of verapamil, the tonic component was markedly inhibited and rhythmicity following phasic component was markedly enhanced. Partial depolarization, achieved by increasing K+ concentration in the normal Krebs by two-fold i.e., to 11.8 mM, enhanced the responses of ATP, noradrenaline and the twitch resulted from the single pulse stimulation. The finding that verapamil potentiates the contractile response to exogenously applied ATP, which is believed to be the "noradrenergic" neurotransmitter in the vas deferens, suggests that this is the mechanism through which verapamil potentiates the twitch responses to field stimulation of the nerve supply.(ABSTRACT TRUNCATED AT 250 WORDS)     

Time-Restricted Eating for 12 Weeks Does Not Adversely Alter Bone Turnover in Overweight Adults

Weight loss is a major focus of research and public health efforts. Time-restricted eating (TRE) is shown to be effective for weight loss, but the impact on bone is unclear. Short-term TRE studies show no effect on bone mineral density (BMD), but no study has measured bone turnover markers. This secondary analysis examined the effect of 12 weeks of TRE vs. unrestricted eating on bone turnover and BMD. Overweight and obese adults aged 18–65 y (n = 20) were randomized to TRE (ad libitum 8-h eating window) or non-TRE. Serum N-terminal propeptide of type I collagen (P1NP), cross-linked N-telopeptide of type I collagen (NTX), and parathyroid hormone (PTH) levels were measured and dual-energy X-ray absorptiometry (DXA) scans were taken pre- and post-intervention. In both groups, P1NP decreased significantly (p = 0.04) but trended to a greater decrease in the non-TRE group (p = 0.07). The treatment time interaction for bone mineral content (BMC) was significant (p = 0.02), such that BMC increased in the TRE group and decreased in the non-TRE group. Change in P1NP was inversely correlated with change in weight (p = 0.04) overall, but not within each group. These findings suggest that TRE does not adversely affect bone over a moderate timeframe. Further research should examine the long-term effects of TRE on bone.     

Retropharyngeal cystic hygroma

Retropharyngeal cystic hygroma is a rare condition and needs to be differentiated from common clinical condition of retropharyngeal abscess. Two such cases are discussed in the present report.     

Primary angiitis of CNS : neuropathological study of three autopsied cases with brief review of literature

Primary angiitis of CNS(PACNS) or granulomatous angiitis of CNS is a rare inflammatory disease of small blood vessels mostly confined to the CNS. The clinical and pathological features of 3 autopsied cases are described. Clinically all the three PACNS patients were young males, age ranging from 19 to 31 years. All presented with varied neurological manifestations. There was no evidence of systemic disease in any of the cases. The ESR was normal and CSF analysis showed chronic meningitic pattern. The cerebral angiogram in one case was normal and the CT scan done in another case showed multiple intracerebral haematoma due to vasculitis. Brain biopsy was not done. Diagnosis was made at post-mortem examination. Histology showed characteristic but variable degree of granulomatous and non-granulomatous angiitis of small vessels. Venulitis with parenchymal haemorrhages was the predominant feature and in one case phlebitis with thrombosis was noted. Since the disease responds to steroids and immunosuppressive therapy, establishing antemortem diagnosis is important. In view of the association of angiitis of CNS with bacteria and viral infections, their role in the evolution of the disease needs to be investigated.     

Basaloid squamous cell carcinoma - larynx

Basaloid squamous cell carcinoma is a rare variant of squamous cell carcinoma, Larynx has been an uncommon site of this tumour which is said to have aggressive biological behaviour with high incidence of cervical and distant metastasis along with second primary. Two cases of laryngeal basaloid squamous cell carcinoma are reported with relevant review of literature. The submucosal spread of tumour is highlighted alongwith role of preoperative radio therapy.     

Survival patterns in treated cases of carcinoma larynx in north india - a 10 years followup study

Conclusion  Patients with stage I and II tumors had the best results with radical radiotherapy alone 5 years survival for patients with stage I and stage II tumors was 90-95% and 75-85% respectively Patients with advanced stage III & IV disease were treated Unoperable stage IV cancer patients had poor outcome and received only palliative treatment     

Overview of fungal rhinosinusitis

The incidence of fungal rhinosinusitis has increased to such extent in recent years that fungal infection should be considered in all patients with chronic rhino sinusitis. In India though the disease was reported earlier only from northern regions of this country, nowadays the disease is increasingly diagnosed from other parts as well. The disease has been categorized with possible five types: acute necrothing (fulminant), chronic invasive, chronic granulomatous invasive, fungal hall (sinus mycetoma), allergic. The first three types are tissue-invasive and the last two are non-invasive fungal rhinosinusitis. However, the categorization is still controversial and open to discussion. Chronic fungal rhinosinusitis can occur in otherwise healthy host and Aspergillus flavus is the common etiological agent in Indian scenario. The pathophys iologic mechanism of the disease remains unclear. It may represent an allergic IgE response, a cell-mediated reaction, or a combination of two. Early diagnosis may prevent multiple surgical procedures and lead to effective treatment. Histopathology and radio-imaging techniques help to distinguish different types and delineate extension of disease process. Culture helps to identify the responsible etiological agent. The presence or absence oj precipitating antibody correlates well with disease progression or recovery. The most immediate need regarding management is to establish the respective roles of surgery and antifungal therapy. Non-invasive disease requires surgical debridement and sinus ventilation only, though, additional oral or local corticosterold therapy may be beneficial in allergie type. For invasive disease, the adjuvant medical therapy is recommended to prevent recurrence and further extension. Itraconazole has been found as an effective drug in such situation. Patients with acute neerotizing type require radical surgery and amphotericin B therapy.