The management of menopausal symptoms in women following treatment for cancer at a specialist menopause service.

OBJECTIVE: The aim of this study was to identify prescribing patterns at a specialist menopause service in a central London teaching hospital for women following treatment for a malignancy. STUDY DESIGN: This was a prospective cohort study with data collected over a seven-month period from December 2019 to June 2020. All women reviewed at the specialist menopause services following treatment of a malignancy, BRCA carriers and Lynch syndrome were included in the study, with management options divided into three categories: hormonal, non-hormonal and no treatment. MAIN OUTCOME MEASURES: The primary outcome of this study was to identify prescribing patterns for all women reviewed following a diagnosis of a malignancy, as well as those with genetic mutations necessitating risk-reducing prophylactic bilateral salpingo-oopherectomy (BSO). RESULTS: Altogether 71 women were included in this study, with the majority of women post management of a non-gynaecological malignancy (51/71, 72%), of which breast cancer was the most common (37/71, 52%). While non-hormonal treatment was the most popular among those treated for breast cancer, for all other malignancies, hormonal treatment was more widespread. Fourteen women also had genetic mutations, with all of these women commencing hormonal treatment post risk reducing surgery. CONCLUSION: With the exception of those with a history of hormone-sensitive breast cancer, the use of hormonal treatment for menopausal symptoms remained widespread. While this was a relatively small study, the need for long-term follow-up across specialist menopause services, to assess the risk of recurrence is vital.

Dietary supplementation of vitamin C: an effective measure for protection against UV-B irradiation using fish as a model organism.

The development of UV-B protective mechanisms in aquacultural species is essential for the sustainable production of healthy aqua crop. Freshwater carp Catla catla larvae (13.5 ± 1.12 mg) were fed with a diet containing 0.5% vitamin C (D1) and a control diet (D2) for 40 days. Each group was exposed to two doses of UV-B irradiation: 360 (5 min, D15 min and D25 min) and 720 mJ cm-2 (10 min, D110 min and D210 min) for 15 days. Significantly (p < 0.05) higher survival and average weight were recorded in D1 compared to D2 exposed to the same dose. Also, significantly (p < 0.001) higher nitric oxide synthase and lower thiobarbituric acid reactive substances and heat shock protein 70 levels were recorded in D15 min compared to the other groups. A direct relationship was found between the dose of UV-B and DNA fragmentation in muscles. DNA damage indices such as tail DNA, tail extent moment and olive tail moment were significantly (p < 0.01) lower in D15 min. Thus, supplementation of vitamin C in the diet provides UV-B protection to larvae.

Effect of dietary supplementation with Achyranthes aspera seed on larval rohu Labeo rohita challenged with Aeromonas hydrophila.

Larval rohu Labeo rohita were fed four different diets: three of the diets contained Achyranthes aspera (prickly chaff-flower) seeds at 0.10% (D1), 0.25% (D2), or 0.50% (D3); the fourth diet was a control diet (D4; no A. aspera supplementation). After 70 d, the rohu were injected intraperitoneally with live Aeromonas hydrophila. Mortality of fish was recorded for 7 d. In the D4 group, the first mortality was observed within 12 h of exposure, whereas in the D1-D3 treatment groups, mortality was first observed at 24 h postexposure. In the D4 group, 50% of fish died within 72 h of exposure, whereas in the D3 group, 10-15% mortality occurred between 72 and 84 h. The cumulative mortality rate was 50% for D4, 40% for D1, 35% for D2, and 15% for D3. Total tissue protein level in the larvae was higher for the D2 and D3 groups than for the other groups. Glutamic oxaloacetic transaminase, glutamate pyruvate transaminase, and thiobarbituric acid reactive substance levels were significantly lower in D3 larvae than in the other groups, whereas lysozyme and nitric oxide synthase levels were significantly higher in D3 larvae compared with the other groups. Dietary supplementation with A. aspera seeds at the 0.50% level provided protection against oxidative stress, prevented tissue damage, and enhanced disease resistance in rohu larvae.

Possible roles of protein kinase A in cell motility and excystation of the early diverging eukaryote Giardia lamblia.

Since little is known of how the primitive protozoan parasite, Giardia lamblia, senses and responds to its changing environment, we characterized a giardial protein kinase A (gPKA) catalytic subunit with unusual subcellular localization. Sequence analysis of the 1080-base pair open reading frame shows 48% amino acid identity with the cyclic AMP-dependent kinase from Euglena gracilis. Northern analysis indicated a 1.28- kilobase pair transcript at relatively constant concentrations during growth and encystation. gPKA is autophosphorylated, although amino acid residues corresponding to Thr-197 and Ser-338 of human protein kinase A (PKA) that are important for autophosphorylation are absent. Kinetic analysis of the recombinant PKA showed that ATP and magnesium are preferred over GTP and manganese. Kinase activity of the native PKA has also been detected in crude extracts using kemptide as a substrate. A myristoylated PKA inhibitor, amide 14-22, inhibited excystation with an IC(50) of 3 microm, suggesting an important role of gPKA during differentiation from the dormant cyst form into the active trophozoite. gPKA localizes independently of cell density to the eight flagellar basal bodies between the two nuclei together with centrin, a basal body/centrosome-specific protein. However, localization of gPKA to marginal plates along the intracellular portions of the anterior and caudal pairs of flagella was evident only at low cell density and higher endogenous cAMP concentrations or after refeeding with fresh medium. These data suggest an important role of PKA in trophozoite motility during vegetative growth and the cellular activation of excystation.

Novel euglycemic and hypolipidemic agents. 1.

A series of [[(heterocyclyl)ethoxy]benzyl]-2,4-thiazolidinediones have been synthesized by the condensation of corresponding aldehyde 1 and 2,4-thiazolidinedione followed by hydrogenation. Both unsaturated thiazolidinedione 2 and its saturated counterpart 3 have shown antihyperglycemic activity. Many of these compounds have shown superior euglycemic and hypolipidemic activity compared to troglitazone (CS 045). The indole analogue DRF-2189 (3g) was found to be a very potent insulin sensitizer, comparable to BRL-49653 in genetically obese C57BL/6J-ob/ob and 57BL/KsJ-db/db mice. Pharmacokinetic and tissue distribution studies conducted on BRL-49653 and DRF-2189 (3g) indicate that these drugs are well-distributed in target tissues. On the basis of euglycemic activity as well as enhanced selectivity against reduction of triglycerides in plasma, DRF-2189 (3g) has been selected for further evaluation.

Glutamine nutrition and metabolism: where do we go from here ?

Glutamine, a "nonessential" amino acid, is attracting widespread attention because of its relevance to numerous metabolic processes and its potential role in the treatment and prevention of critical illness. In this paper we review some key concepts of glutamine biochemistry, metabolism, and nutrition. We then discuss several studies in the area of glutamine metabolism and nutrition that are primed for further investigation.

Naturally occurring rearranged taxoids.

The rearranged taxoids have recently been reported from different Taxus species. The literature concerning the chemistry, biogenesis, and bioactivity of such compounds is reviewed.

Quantitative evaluation of large granular lymphocytes in mice on ascorbic acid supplement diet.

The mechanism of ascorbic acid as an immunostimulatory agent is still clearly unknown. It is speculated in the present study that the host resistance may be due in part to ascorbic acid potentiation of the host immune system through stimulation and activation large granular lymphocytes.

Glucocorticoids regulate intestinal glutamine synthetase gene expression in endotoxemia.

PURPOSE: Although glutamine is required to maintain gut mucosal metabolism and function, intestinal glutamine uptake from the gut lumen and from the bloodstream is decreased during sepsis. We hypothesized that endogenous mucosal glutamine biosynthesis is increased during endotoxemia, and we attempted to define the "stress" mediators that regulate the activity of small intestinal glutamine synthetase (GS), the principal enzyme of de novo glutamine biosynthesis in the gut. METHODS: Adult rats received Escherichia coli lipopolysaccharide (LPS) (7.5 mg/kg intraperitoneally), RU 38486 (a glucocorticoid antagonist; 10 mg/kg by gavage) 2 hours prior to LPS administration, antibody to tumor necrosis factor (TNF) (4 mg/kg intraperitoneally) prior to LPS administration, or ketorolac tromethamine (a prostaglandin synthesis inhibitor; 1 mg/kg intraperitoneally) followed by LPS administration. Mucosal GS activity was assayed 12 hours after LPS administration. In a separate set of studies, cultured intestinal mucosal cells (Caco-2) were exposed to LPS, interleukin 1 (IL-1), IL-6, TNF-alpha, interferon-gamma, prostaglandin E2, or dexamethasone. Twelve hours later, GS activity was assayed and messenger RNA was extracted. The GS transcripts were labeled with a GS complementary DNA probe radiolabeled with phosphorus 32, were quantitated by phosphoimaging, and were normalized to beta-actin. RESULTS: In vivo LPS treatment increased mucosal GS activity by 250%. Pretreatment with antibody to TNF or ketorolac did not inhibit the LPS-induced increase in mucosal GS, whereas pretreatment with RU 38486 attenuated the increase in gut GS activity by 60%. Lipopolysaccharide, IL-1, IL-6, TNF-alpha, gamma-interferon, and prostaglandin E2 did not increase GS activity in Caco-2 cells, whereas dexamethasone increased GS activity and messenger RNA 2.5-fold and threefold, respectively. These data indicate that cytokines and prostaglandins (prostaglandin E2) do not regulate mucosal GS expression during endotoxemia. Glucocorticoids, however, stimulate GS gene expression directly. CONCLUSIONS: This hormonally mediated response may support de novo mucosal GS during septic states when uptake of glutamine from the lumen and blood is decreased.

Uterine cervical dysplasia with reference to the betel quid chewing habit.

Systemic effects of betel quid are poorly documented compared to its local effects on the mucosa of the oral cavity and pharynx. In the present study dysplastic activity of the betel quid on exfoliated uterine cervical cells was studied and compared with women addicted to other habits or nothing. That the mutagenic changes at cellular level are associated with prolonged use of betel quid is suggested.