Effect of diet on oxidation of 17 beta-estradiol in vivo

The effect of a high fat, low carbohydrate, low protein diet on the in vivo oxidation of 17 beta-estradiol was studied using radiometric methods. Five male chimpanzees were fed a normal (13%) fat diet or a high (65%) fat diet for 8 weeks. After a 4-week rest period, the animals were fed the alternative diet. The mean percent oxidation of 16 alpha-[3H]estradiol-17 beta 24 h after injection was 3.8 +/- 1.3% (+/- SD) on the normal diet vs. 18.4 +/- 4.7% on the high fat diet (P less than 0.01). In contrast, the mean percent oxidation of 2-[3H]estradiol 24 h after injection was 31.6 +/- 3.8% (+/- SD) on the normal diet vs. 20.0 +/- 3.5% on the high fat diet (P less than 0.05). These results suggest that the oxidation of 17 beta-estradiol to estriols relative to that to catechol estrogens is increased by a high fat diet.     

Mechanisms involved in the regulation of bovine pulmonary vascular tone by the 5-HT1B receptor

Background and purpose:

5-HT_1B receptors may have a role in pulmonary hypertension. Their relationship with the activity of BK_Ca, a T-type voltage-operated calcium channel (VOCC) and cyclic nucleotide-mediated relaxation was examined.

Experimental approach:

Ring segments of bovine pulmonary arteries were mounted in organ baths in modified Krebs–Henseleit buffer (37^oC) under a tension of 20 mN and gassed with 95% O₂/5% CO₂. Isometric recordings were made using Chart 5 software.

Key results:

Contractile responses to 5-HT (10 nM–300 µM) were inhibited similarly by the 5-HT_1B receptor antagonist SB216641 (100 nM) and the T-type VOCC blockers mibefradil (10 µM) and NNC550396 (10 µM) with no additive effect between SB216641 and mibefradil. Inhibition by SB216641 was prevented by the potassium channel blocker, charybdotoxin (100 nM). 5-HT_1B receptor activation and charybdotoxin produced a mibefradil-sensitive potentiation of responses to U46619. Bradykinin (0.1 nM–30 µM), sodium nitroprusside (0.01 nM–3 µM), zaprinast (1 nM–3 µM), isoprenaline (0.1 nM–10 µM) and rolipram (1 nM–3 µM) produced 50% relaxation of arteries constricted with 5-HT (1–3 µM) or U46619 (30–50 nM) in the presence of 5-HT_1B receptor activation, but full relaxation of arteries constricted with U46619, the 5-HT_2A receptor agonist 2,5 dimethoxy-4 iodoamphetamine (1 µM) or 5-HT in the presence of 5-HT_1B receptor antagonism. Enhanced relaxation of 5-HT-constricted arteries by cGMP-dependent pathways, seen in the presence of the 5-HT_1B receptor antagonist, was reversed by charybdotoxin whereas cAMP-dependent relaxation was only partly reversed by charybdotoxin.

Conclusions and implications:

5-HT_1B receptors couple to inhibition of BK_Ca, thus increasing tissue sensitivity to contractile agonists by activating a T-type VOCC and impairing cGMP-mediated relaxation. Impaired cAMP-mediated relaxation was only partly mediated by inhibition of BK_Ca.     

Prevalence of internet addiction among college students in the Indian setting: a systematic review and meta-analysis

BackgroundThe internet is an integral part of everyone’s life. College going adolescents are highly vulnerable to the misuse of the internet.AimsTo estimate the pooled prevalence of internet addiction (IA) among college students in India.MethodsLiterature databases (PubMed, Web of Science, Scopus, EMBASE, PsycINFO and Google Scholar) were searched for studies assessing IA using the Young Internet Addiction Test (Y-IAT) among adolescents from India, published in the English language up to December 2020. We included studies from 2010 to 2020 as this is the marked era of momentum in wireless internet connectivity in India. The methodological quality of each study was scored, and data were extracted from the published reports. Pooled prevalence was estimated using the fixed-effects model. Publication bias was evaluated using Egger’s test and visual inspection of the symmetry in funnel plots.ResultsFifty studies conducted in 19 states of India estimated the prevalence of IA and the overall prevalence of IA as 19.9% (95% CI: 19.3% to 20.5%) and 40.7% (95% CI: 38.7% to 42.8%) based on the Y-IAT cut-off scores of 50 and 40, respectively. The estimated prevalence of severe IA was significantly higher in the Y-IAT cut-off points of 70 than 80 (12.7% (95% CI: 11.2% to 14.3%) vs 4.6% (95% CI: 4.1% to 5.2%)). The sampling method and quality of included studies had a significant effect on the estimation of prevalence in which studies using non-probability sampling and low risk of bias (total quality score ≥7) reported lower prevalence. The overall quality of evidence was rated as ‘moderate’ based on the Grading of Recommendations Assessment, Development and Evaluation criteria.ConclusionsOur nationally representative data suggest that about 20% to 40% of college students in India are at risk for IA. There is a need for further research in the reconsideration of Y-IAT cut-off points among Indian college students.PROSPERO registration numberCRD42020219511.     

Double-blind, randomized, placebo-controlled trial of a cream containing the Stryphnodendron adstringens (Martius) Coville bark extract for suppressing terminal hair growth

Background  Excess of terminal hair can be defined as excessive hair that appears in male-like pattern in women. Some experts consider this condition as a result of an atypical relationship between levels of circulating androgens and sensitivity of androgen receptors in hair follicles to circulating androgens.
Aims  The aim of this research work was to evaluate the efficacy of a topical treatment for suppressing terminal hair growth of a cream containing 6.0% of the Stryphnodendron adstringens bark extract.
Study design and subjects  Study was randomized, double-blind and placebo-controlled. Subjects with excess of terminal hair were randomized to placebo and to the active treatment (cream with 6.0% of the extract). Evaluation was performed before and after 6 months, and subjects were photographed in each time. Clinical examination was carried out with the same physicians and in accordance with the Ferriman-Gallwey (FG) score.
Results  Benefits of the cream containing S. adstringens bark extract was observed in 60.98% ( P <  0.001) of the subjects. FG score changed from 4 to 3 in the placebo group compared to 4–2 in the active. The cream suppressed the terminal hair growth and diminished the number of terminal hair. Subjects also described the reduction of skin hyperpigmentation, folliculitis and acne. Adverse events were not verified by physicians or patients.
Conclusions  The cream with 6.0% of the S. adstringens bark extract was effective on the reduction and on the reversion of the terminal hair excess, being considered a new promissory product for such finality .     

Chondroblastoma patella presenting as a pathological fracture

A 24-year-old male presented with an inability to walk after a trivial fall. He had pain and mild swelling anterior to the right knee for the past one year. X-ray showed a transverse fracture of patella with a lytic lesion occupying most of the two halves of the patella. Fine needle aspiration cytology (FNAC) of the lytic lesion revealed a few osteoclastic giant cells and occasional osteoblasts against a hemorrhagic background. Patellectomy was performed. Histology revealed trabecular bone admixed with proliferating chondroid tissue at places admixed with myxoid and fibrous tissue with focal areas of calcification suggestive of chondroblastoma. Focal areas showed osteoclastic giant cells with areas of hemorrhage. The purpose is to present a rare tumor occurring at an unusual site which presented as pathological fracture.     

Acute exposure to the nutritional toxin alcohol reduces brain protein synthesis in vivo

Few studies have measured brain protein synthesis in vivo using reliable methods that consider the precursor pool, and there is a paucity of data on the regional sensitivity of this organ to nutritional or toxic substances. We hypothesized that different areas of the brain will exhibit variations in protein synthesis rates, which might also be expected to show different sensitivities to the nutritional toxin, ethanol. To test this, we dosed male Wistar rats with ethanol (75 mmol/kg body weight) and measured rates of protein synthesis (ie, the fractional rate of protein synthesis, defined as the percentage of the protein pool renewed each day; k(s), %/d) in different brain regions 2.5 hours later with the flooding dose method using L-[4-(3)H] phenylalanine. In the event that some regions were refractory to the deleterious effects of ethanol, we also predosed rats with cyanamide, an aldehyde dehydrogenase inhibitor (ie, cyanamide + ethanol), to increase endogenous acetaldehyde, a potent neurotoxic agent. The results indicated the mean fractional rates of protein synthesis in the cortex was 21.1%/d, which was significantly lower than either brain stem (30.2%/d, P <.025), cerebellum (30.1%/d, P <.01), or midbrain (29.8%, P <.025). Ethanol significantly decreased protein synthesis in the cortex (21%, P < 0.01), cerebellum (19%, P <.025), brain stem (44%, P <.025), but not in the midbrain (not significant [NS]). However, significant reductions in protein synthesis in the midbrain occurred in cyanamide + ethanol-dosed rats (60%, P <.0001). Cyanamide + ethanol treatment also reduced k(s) in the brain stem (66%, P <.001), cortex (59%, P <.001), and cerebellum (55%, P <.001). In conclusion, the applicability of the flooding dose technique to measure protein synthesis in the brain in vivo is demonstrated by its ability to measure regional difference. Impaired protein synthesis rates may contribute to or reflect the pathogenesis of alcohol-induced brain damage.     

Extrasplanchnic effect of sulfobromophthalein (BSP) on plasma estrogen levels in the dog.

The effect of the drug sulfobromophthalein (BSP) on plasma estrogens in the dog were studied during intravenous infusions of 3H-labeled estrogens. During [3H]estrone infusion, BSP administration caused a marked increase in arterial plasma levels of the radioactive conjugated estrogens, estrone glucosiduronate, estradiol-17 beta glucosiduronate(s), and estrone sulfate. Levels of the unconjugated estrogens, estrone and estradiol-17 beta, were substantially unaltered. Possible mechanisms were investigated. Splanchnic extraction of the conjugates did not change significantly during BSP administration, and renal excretion rose promptly in proportion to the plasma levels, thus virtually excluding decreased biliary or renal excretion. There was no net discharge of estrogen glucosiduronate radioactivity from adipose tissue or muscle following BSP. During [3H]estrone glucosiduronate infusion, BSP again caused an increase in plasma estrone glucosiduronate, thus excluding increased formation (of this conjugate, at least). BSP caused decreased extraction of estrone glucosiduronate by the hindlimb, indicating that decreased metabolism was the probable cause of the elevated plasma levels. BSP also caused decreased formation of unconjugated estrogens by the lungs, indicating that the decreased metabolism includes decreased hydrolysis of estrogen glucosiduronates.     

Acute dosage with dexrazoxane, but not doxorubicin, is associated with increased rates of hepatic protein synthesis in vivo.

An investigation was carried out into the effects of dexrazoxane and doxorubicin on hepatic protein synthesis in vivo. The protocol included 8 groups of rats and involved a pretreatment stage of 30 min followed by a treatment stage of either 2.5 or 24 h. Male Wistar rats (=0.15-0.20 kg) were pretreated with either dexrazoxane (100 mg/kg; 5 ml/kg) or saline (0.15 mol/l NaCl; 5 ml/kg). At 30 min after the pretreatment, rats were again injected with either doxorubicin (5 mg/kg; 10 ml/kg) or saline (0.15 mol/l NaCl; 10 ml/kg) in the treatment phase. Rats were sacrificed at either 2.5 or 24 h after the last doxorubicin or saline injection. Rate of protein synthesis were measured 10 min prior to sacrificing rats, with a flooding dose of L-[4-3H]phenylalanine. Liver was analyzed for the protein synthetic capacity (Cs, mg RNA/g protein), the fractional rate of protein synthesis (k(s), %/d), and the RNA activity (kRNA mg protein/d/mg RNA). Complementary analysis included plasma albumin, total protein and activities of alkaline phosphatase, and aspartate aminotransferase. In the 2.5-h study, doxorubicin alone had no effect on any of the above variables. Dexrazoxane alone increased Cs, k(s) and kRNA at 2.5 h. Combined dexrazoxane + doxorubicin increased hepatic Cs and k(s) with concomitant reductions in total plasma protein. In the 24-h study, doxorubicin alone had no effect on any of the variables. Dexrazoxane alone had no effect on either Cs, k(s), or kRNA but raised plasma activities of alkaline phosphatase and aspartate aminotransferase. Combined dexrazoxane + doxorubicin increased Cs and k(s) and decreased total plasma protein and increased plasma aspartate aminotransferase activities at 24 h. In conclusion, there is no evidence that acutely doxorubicin per se has measurable effects on hepatic protein synthesis in vivo in an acute period. However, acutely dexrazoxane increases hepatic protein synthesis, which may represent its putative cytotoxic effects, as indicated by raised serum activities of liver enzymes. A combination of both dexrazoxane + doxorubicin appears to have a greater effect in increasing liver protein synthesis than dexrazoxane alone.