Effect of lycoriside,an acylglucosyloxy alkaloid,on mast cells

The effect of lycoriside, an acylglucosyloxy alkaloid from Crinum asiaticum Linn, (family Amaryllidaceae), with or without sitosterol-3-O--D-glucoside, was studied on the rate of degranulation of peritoneal mast cells of albino rats. Lycoriside, at lower concentrations (1–20 µg/ml), in vitro, produced statistically significant protection against Tween 80-induced degranulation, as also to sensitized mast cells challenged with an antigen (horse serum). It also provided protection against compound 48/80-induced degranulation of mast cells when administered in vivo (1–5 mg/kg, po). At higher concentrations (100 µg/ml and above), in vitro, however, it had a mast-cell degranulation effect per se. The addition of sitosterol-3-O--D-glucoside to lycoriside did not modify the effect of the latter compound. The mechanism of the dual response elicited by lycoriside is appraised in view of a concentration-dependent anti- or prerelease effect on mast-cell mediators.     

Management of Neglected Upper Cervical Spine Injuries

BackgroundInjuries involving upper cervical spine are serious and fatal injuries which are associated with alteration of normal occipital–cervical anatomy. These injuries may result in permanent neurologic deficits or neck deformity if not treated in a timely and appropriate manner.ObjectiveTo evaluate the outcomes of neglected upper cervical spine injuries treated by various methods.Study designRetrospective study.Materials and methodsTwelve patients attending ER or OPD with a history of neck trauma and who were diagnosed with fractures and fracture dislocations C1 and C2 were included in the study. Fresh injuries sustained within a week were excluded from study. The outcomes were measured in terms of improvement in VAS, ODI Scores and correction of the neck deformity. Surgical parameters like duration of surgery and blood loss were also observed.ResultsEleven males and one female. The mean age was 40.9 ± 16.9 (07–67 years). Eleven patients underwent posterior instrumentation, while one patient was treated anteriorly. The mean delay in presentation was 28 ± 8.67 days (15–42 days). The mean duration of surgery was 188.3 ± 34.35 min (120–240 min), average blood loss was 350 ± 111.8 ml (150–600 ml). The mean VAS improved from 8.45 ± 0.89 to 3.9 ± 0.51 (p < 0.05). The mean ODI Pre-operatively was 88.45 ± 5.89 which improved to 31.9 ± 4.01 (p < 0.05). The neck deformity/torticollis was corrected in all the patients.ConclusionsNeglected upper cervical spine injuries are difficult to treat and a posterior approach is helpful in reducing the subluxations indirectly and to obtain a posterior fusion.     

Response of the ENPP1-Deficient Skeletal Phenotype to Oral Phosphate Supplementation and/or Enzyme Replacement Therapy: Comparative Studies in Humans and Mice

Inactivating mutations in human ecto-nucleotide pyrophosphatase/phosphodiesterase-1 (ENPP1) may result in early-onset osteoporosis (EOOP) in haploinsufficiency and autosomal recessive hypophosphatemic rickets (ARHR2) in homozygous deficiency. ARHR2 patients are frequently treated with phosphate supplementation to ameliorate the rachitic phenotype, but elevating plasma phosphorus concentrations in ARHR2 patients may increase the risk of ectopic calcification without increasing bone mass. To assess the risks and efficacy of conventional ARHR2 therapy, we performed comprehensive evaluations of ARHR2 patients at two academic medical centers and compared their skeletal and renal phenotypes with ENPP1-deficient Enpp1^asj/asj mice on an acceleration diet containing high phosphate treated with recombinant murine Enpp1-Fc. ARHR2 patients treated with conventional therapy demonstrated improvements in rickets, but all adults and one adolescent analyzed continued to exhibit low bone mineral density (BMD). In addition, conventional therapy was associated with the development of medullary nephrocalcinosis in half of the treated patients. Similar to Enpp1^asj/asj mice on normal chow and to patients with mono- and biallelic ENPP1 mutations, 5-week-old Enpp1^asj/asj mice on the high-phosphate diet exhibited lower trabecular bone mass, reduced cortical bone mass, and greater bone fragility. Treating the Enpp1^asj/asj mice with recombinant Enpp1-Fc protein between weeks 2 and 5 normalized trabecular bone mass, normalized or improved bone biomechanical properties, and prevented the development of nephrocalcinosis and renal failure. The data suggest that conventional ARHR2 therapy does not address low BMD inherent in ENPP1 deficiency, and that ENPP1 enzyme replacement may be effective for correcting low bone mass in ARHR2 patients without increasing the risk of nephrocalcinosis. © 2021 American Society for Bone and Mineral Research (ASBMR).     

ANEURYSM OF SINUS OF VALSALVA DISSECTING INTO THE INTERVENTRICULAR SEPTUM – ECHOCARDIOGRAPHIC DIAGNOSIS (A Case Report)

Aneurysm of sinus of Valsalva dissecting into interventricular septum is a rare entity. We report one such case who was incidentally diagnosed by echocardiography to have this abnormality during evaluation of a clinically suspected isolated aortic regurgitation.KEY WORDS: Aneurysm – dissecting – sinus of Valsalva, Echocardiography     

Complete nucleotide sequence of mouse mammary tumor virus from jyg chinese wild mice: Absence of bacterial insertion sequences in the cloned viral gag gene

Mammary tumors of a newly isolated strain of Chinese wild mouse (JYG mouse) harbor exogenous mouse mammary tumor virus (MMTV). The complete nucleotide sequence of exogenous JYG-MMTV was determined on the proviral 5' long terminal repeat (LTR)(partial)-gag-pol-env-3' LTR (partial) fragment cloned into a plasmid vector and the cDNA sequence from JYG-MMTV producing cells. Similarly to the other MMTV species the LTR of JYG-MMTV contains an open reading frame (ORF). The amino acid sequence of the JYG-MMTV ORF resembles that of SW-MMTV (92% identity) and endogenous Mtv-7 (93% identity) especially at the C-terminal region. Thus, a functional similarity in T-cell receptor V beta recognition as a superantigen is implicated among these MMTV species. Analysis of the viral gag nucleotide sequence revealed that this gene is not disrupted by the bacterial insertion sequence IS1 or IS2, which have been reported to be present in the majority of the plasmids containing the gag region. Comparison of amino acid sequences of JYG-MMTV with those of BR6-MMTV showed that over 96% of the amino acids of gag, pol, protease and env products are identical. These results suggest the intact nature of the nucleotide sequence of the near full-length MMTV genome cloned in the plasmid.     

Estrogen augments hypothalamicβ-endorphin secretion and activates an inhibitoryβ-endorphin short-loop feedback system

The role of estrogen in the regulation of hypothalamicβ-endorphin hormone secretion is studied by determiningβ-endorphin concentration in pituitary portal plasma of ovariectomized rats in the presence or absence of this steroid and/or the opioid antagonist naloxone. Twenty-six hours following s.c. injection of 10 /μg estradiol benzoate (estrogen) or oil, rats anesthetized with Saffan (alphaxolone/alphadolone) underwent pituitary stalk exposure and hypophysectomy, after which pituitary portal blood was continuously collected and stored in 15 min aliquots from 1100-1400 h. At 1100 h, animals were given an initial bolus iv injection of naloxone or saline (naloxone, 2 mg/ kg, or saline, 0.1 ml) and then infused (iv) continuously with naloxone (2 mg/kg/h) or saline (0.8 ml/h) until 1400 h. Plasma samples were extracted and assayed by radioimmunoassay forβ-endorphin. Treatment with estrogen increased the meanβ-endorphin levels twofold as compared to oil-treated controls. Naloxone potentiated estrogen action ofβ-endorphin secretion, but did not affect basalβ-endorphin secretion. These results suggest that estrogen enhancedβ-endorphin secretion from the hypothalamus. Furthermore, the hypersecretion ofβ-endorphin induced by naloxone with, but not without, estrogen supports the existence of an estrogen-activated short-loop negative feedback mechanism regulatingβ-endorphin secretion.     

Potentiation of the mitogenic effect of estrogen on the pituitary-gland by alcohol-consumption

The effect of alcohol on estrogen-regulated lactotropic cell proliferation was examined in Fisher 344 rats. Alcohol was administered for 2 weeks using liquid diet containing 8.7% ethanol (v/v) and 37% ethanol-derived calories. The control group was pair-fed with an isocaloric diet minus the ethanol or adlib-fed with normal diet. Ethanol-treated rats showed mean blood ethanol concentrations between 60-90 mg/dl. Alcohol treatment did not effect the body growth rate, but increased the DNA synthesis in lactotropes and reduced the levels of lactotropic growth inhibitory transforming growth factor-beta 1 (TGF-beta 1) protein and mRNA in the pituitary. These results suggest that alcohol promotes estrogen-induced lactotropic proliferation, possibly by down regulating the inhibitory TGF-beta 1 control of lactotropic function.