Brain histamine metabolism in transmissible spongiform encephalopathy (Scrapie)

Summary The histamine (Hi) content and the activity of L-histidine decarboxylase (HD) in brains of scrapie infected hamsters were measured. No significant changes in Hi levels in particular brain areas were found when compared to controls. Decreased activity of HD was found in hypothalamus (p<0.02). Increased activity of the enzyme was observed in rest of brain, which consisted mainly of thalamus and striatum (p<0.05).     

Botanicals in Postmenopausal Osteoporosis

Osteoporosis is a systemic bone disease characterized by reduced bone mass and the deterioration of bone microarchitecture leading to bone fragility and an increased risk of fractures. Conventional anti-osteoporotic pharmaceutics are effective in the treatment and prophylaxis of osteoporosis, however they are associated with various side effects that push many women into seeking botanicals as an alternative therapy. Traditional folk medicine is a rich source of bioactive compounds waiting for discovery and investigation that might be used in those patients, and therefore botanicals have recently received increasing attention. The aim of this review of literature is to present the comprehensive information about plant-derived compounds that might be used to maintain bone health in perimenopausal and postmenopausal females.     

Curcumin and Its Potential Impact on Microbiota

Curcumin is one of the most frequently researched herbal substances; however, it has been reported to have a poor bioavailability and fast metabolism, which has led to doubts about its effectiveness. Curcumin has antioxidant and anti-inflammatory effects, and has demonstrated favorable health effects. Nevertheless, well-reported in vivo pharmacological activities of curcumin are limited by its poor solubility, bioavailability, and pharmacokinetic profile. The bidirectional interactions between curcumin and gut microbiota play key roles in understanding the ambiguity between the bioavailability and biological activity of curcumin, including its wider health impact.     

Anti-SARS-CoV-2 activity of targeted kinase inhibitors: Repurposing clinically available drugs for COVID-19 therapy

Coronavirus disease 2019 (COVID-19) remains a major public health concern, and vaccine unavailability, hesitancy, or failure underscore the need for discovery of efficacious antiviral drug therapies. Numerous approved drugs target protein kinases associated with viral life cycle and symptoms of infection. Repurposing of kinase inhibitors is appealing as they have been vetted for safety and are more accessible for COVID-19 treatment. However, an understanding of drug mechanism is needed to improve our understanding of the factors involved in pathogenesis. We tested the in vitro activity of three kinase inhibitors against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), including inhibitors of AXL kinase, a host cell factor that contributes to successful SARS-CoV-2 infection. Using multiple cell-based assays and approaches, gilteritinib, nintedanib, and imatinib were thoroughly evaluated for activity against SARS-CoV-2 variants. Each drug exhibited antiviral activity, but with stark differences in potency, suggesting differences in host dependency for kinase targets. Importantly, for gilteritinib, the amount of compound needed to achieve 90% infection inhibition, at least in part involving blockade of spike protein-mediated viral entry and at concentrations not inducing phospholipidosis (PLD), approached a clinically achievable concentration. Knockout of AXL, a target of gilteritinib and nintedanib, impaired SARS-CoV-2 variant infectivity, supporting a role for AXL in SARS-CoV-2 infection and supporting further investigation of drug-mediated AXL inhibition as a COVID-19 treatment. This study supports further evaluation of AXL-targeting kinase inhibitors as potential antiviral agents and treatments for COVID-19. Additional mechanistic studies are needed to determine underlying differences in virus response.     

Telomeric length variation in human testicular germ cell tumours

Telomeric length was studied in 5 cases of human testicular germ cell rumours by measuring the length of the terminal restriction fragments (TRFs) containing the (TTAGCG)(n) sequence. Mean TRF length in human placenta used as a source of reference DNA for assessing the effect of cellular ageing was 14 kbp. TRF length in two classical seminomas and a mixed embryonal carcinoma/atypical seminoma ranged from 4 to 14 kbp and from 4 to 23 kbp, respectively, with the same mean value of 9 kbp in both tumour types. In a mixed teratoma/embryonal carcinoma, telomeric length ranged from 14 to 27 kbp with a mean of 20 kbp. In the single case of spermatocytic seminoma studied, telomeric length was up to 100 kbp with a distinct sharp band at similar to 50 kbp, representing the longest, homogeneous telomeres found so far.     

Spatial games and the maintenance of cooperation.

The Prisoner's Dilemma (PD) is a widely employed metaphor for problems associated with the evolution of cooperative behavior. We have recently proposed an alternative approach to the PD, by exploring "spatial games" in which players--who are either pure cooperators, C, or pure defectors, D--interact with neighbors in some spatial array; in each generation, players add up the scores from all encounters, and in the next generation a given cell is retained by its previous owner or taken over by a neighbor, depending on who has the largest score. Over a wide range of the relevant parameters, we find that C and D persist together indefinitely (without any of the complex strategies that remember past encounters, and anticipate future ones, which characterize essentially all previous work on the iterated PD). Our earlier work, however, dealt with symmetric spatial lattices in two dimensions, deterministic winning and discrete time. We show here that the essential results remain valid in more realistic situations where the spatial distributions of cells are random in two or three dimensions, and where winning is partly probabilistic (rather than being determined by the largest local total). The essential results also remain valid (pace Huberman and Glance [Huberman, B. A. & Glance, N. S. (1993) Proc. Natl. Acad. Sci. USA 90, 7716-7718]) when interactions occur in continuous rather than discrete time.     

The smoking cessation efficacy of varying doses of nicotine patch delivery systems 4 to 5 years post-quit day

BACKGROUND: This study was undertaken to evaluate the long-term smoking cessation efficacy of varying doses of transdermal nicotine delivery systems 4 to 5 years post-quit day. METHODS: A follow-up study was conducted 48 to 62 months after quit day among patients who were enrolled in the Transdermal Nicotine Study Group investigation. The latter study included group smoking cessation counseling and randomized assignment to 21, 14, or 7 mg nicotine patches or placebo patches. Seven of nine smoking cessation research centers participated in the long term follow-up investigation. RESULTS: The self-reported continuous quit rate among patients originally assigned 21 mg (20.2%) was significantly higher than rates for patients assigned 14 mg (10.4%), 7 mg (11.8%), or placebo patches (7.4%). Log rank survival analysis found no difference in relapse rates after 1 year postcessation. Smokers under age 30 years were significantly less likely to be abstinent at long term follow-up compared to smokers > or = 30 years of age (3 vs 13%, respectively). Mean weight gain in confirmed continuous quitters was 10.1 kg in men and 8.0 kg in women. Of the 63 continuous abstainers surveyed, 30 respondents (48%) reported that they no longer craved cigarettes, and no individual reported daily craving for cigarettes. CONCLUSIONS: Nicotine patch therapy with 21 mg/day patches resulted in a significantly higher long-term continuous abstinence rate compared to lower dose patches and placebo. Relapse rates among the various treatment conditions were similar after 1 year postcessation.     

Lack of combined effects of exposure and smoking on respiratory health in aluminium potroom workers

OBJECTIVE: To investigate the combined influence on respiratory health of smoking and exposure in an aluminium potroom. METHODS: In a cross sectional study of 75 potroom workers (23 never smokers, 38 current smokers, 14 ex-smokers) and 56 controls in the same plant (watchmen, craftsmen, office workers, laboratory employees; 18 non-smokers, 21 current smokers, 17 ex-smokers), prevalences of respiratory symptoms and spirometric indices were compared. RESULTS: Smokers in the potroom group had a lower prevalence of respiratory symptoms than never smokers or ex-smokers, which was significant for wheezing (2.6% v 17.4% and 28.6% respectively, both p < 0.01), whereas respiratory symptoms in controls tended to be highest in smokers (NS). No effects of potroom work on the prevalence of respiratory symptoms could be detected. In potroom workers, impairment of lung function due to occupational exposure was found only in non-smokers, with lower results for forced vital capacity (FVC) (98.8% predicted), forced expiratory volume in one second (FEV1) (96.1% predicted) and peak expiratory flow (PEF) (80.2% predicted) compared with controls (114.2, 109.9, and 105.9% predicted; each p < 0.001). Conversely, effects of smoking on lung function were only detectable in non-exposed controls (current smokers v non-smokers: FVC 98.8% v 114.2% predicted; p < 0.01; FEV1 95.5 v 109.9% predicted; p < 0.05). CONCLUSIONS: In a cross sectional survey such as this, the effects of both smoking and occupational exposure on respiratory health may be masked in subjects with both risk factors. This is probably due to strong selection processes which result in least susceptible subjects continuing to smoke and working in an atmosphere with respiratory irritants.