Local injection of a mixture of beta-aminopropionitril fumarate and sodium hyaluronate together with controlled exercise for treatment of subacute superficial digital flexor tendonitis in horses

Local injection of a mixture of beta-aminopropionitril fumarate (BAPN-f) and sodium hyaluronate (NaH⁺) together with controlled exercise were evaluated for treatment of superficial digital flexor tendon (SDFT) injuries in horses. Fourteen mixed breed horses with subacute SDF tendon injuries in forelimbs were randomly assigned to two groups. One group received BAPN-f (0.7 mg/ml) and the other received NaH⁺ (10 mg/ml) all by intratendinous injection. Controlled exercise started during the first week after intratendinous treatment and continued for 12 weeks. Cross-sectional area (CSA) of the SDFT, diameter of the SDFT, and relative area of the lesion (presence of CSA) were measured by ultrasonographic examination. Lesions were semiquantitatively graded for echogenicity on a scale of 0 to 4. The lesion severity in CSA was significantly reduced by BAPN and NaH compared to those horses treated by BAPN only (p < 0.05). Lesion echogenicity score was significantly higher in horses treated with BAPN and NaH⁺ at day 0 compared to horses treated with BAPN (p < 0.05). At the end of the study, lesion echogenicity score was significantly reduced in the horses treated with BAPN and NaH⁺ compared to horses treated by BAPN only (p < 0.05). According to the results of the present study, a combination of BAPN-f and NaH⁺ has a greater beneficial effect on tendon healing and remodeling in horses, as assessed by sonographic examination, compared to treatment with single drugs.     

Kv1 channels selectively prevent dendritic hyperexcitability in rat Purkinje cells

Purkinje cells, the sole output of the cerebellar cortex, encode the timing signals required for motor coordination in their firing rate and activity pattern. Dendrites of Purkinje cells express a high density of P/Q-type voltage-gated calcium channels and fire dendritic calcium spikes. Here we show that dendritic subthreshold Kv1.2 subunit-containing Kv1 potassium channels prevent generation of random spontaneous calcium spikes. With Kv1 channels blocked, dendritic calcium spikes drive bursts of somatic sodium spikes and prevent the cell from faithfully encoding motor timing signals. The selective dendritic function of Kv1 channels in Purkinje cells allows them to effectively suppress dendritic hyperexcitability without hindering the generation of somatic action potentials. Further, we show that Kv1 channels also contribute to dendritic integration of parallel fibre synaptic input. Kv1 channels are often targeted to soma and axon and the data presented support a major dendritic function for these channels.     

Breast cancer risk associated with ovulation-stimulating drugs

BACKGROUND: Despite the recognized role of hormones in the aetiology of breast cancer, there has been little evaluation of hormonal preparations used to treat infertility. METHODS: A retrospective cohort study of 12,193 women evaluated for infertility between 1965 and 1988 at five clinical sites identified 292 in situ and invasive breast cancers in follow-up through 1999. Standardized incidence ratios (SIRs) compared breast cancer risks with those of the general population. Analyses within the cohort estimated rate ratios (RRs) associated with medications after adjustment for other breast cancer predictors. RESULTS: Infertile patients had a significantly higher breast cancer risk than the general population [SIR = 1.29, 95% confidence interval (CI) 1.1-1.4]. Analyses within the cohort showed adjusted RRs of 1.02 for clomiphene citrate and 1.07 for gonadotrophins, and no substantial relationships to dosage or cycles of use. Slight and non-significant elevations in risk were seen for both drugs after > or = 20 years of follow-up (RRs = 1.39 for clomiphene and 1.54 for gonadotrophins). However, the risk associated with clomiphene for invasive breast cancers was statistically significant (RR = 1.60, 95% CI 1.0-2.5). CONCLUSIONS: Although there was no overall increase in breast cancer risk associated with use of ovulation-stimulating drugs, long-term effects should continue to be monitored.     

Curcumin,Quercetin, Catechins and Metabolic Diseases: The Role of Gut Microbiota

Polyphenols (PPs) are the naturally occurring bioactive components in fruits and vegetables, and they are the most abundant antioxidant in the human diet. Studies are suggesting that ingestion of PPs might be helpful to ameliorate metabolic syndromes that may contribute in the prevention of several chronic disorders like diabetes, obesity, hypertension, and colon cancer. PPs have structural diversity which impacts their bioavailability as they accumulate in the large intestine and are extensively metabolized through gut microbiota (GM). Intestinal microbiota transforms PPs into their metabolites to make them bioactive. Interestingly, not only GM act on PPs to metabolize them but PPs also modulate the composition of GM. Thus, change in GM from pathogenic to beneficial ones may be helpful to ameliorate gut health and associated diseases. However, to overcome the low bioavailability of PPs, various approaches have been developed to improve their solubility and transportation through the gut. In this review, we present evidence supporting the structural changes that occur after metabolic reactions in PPs (curcumin, quercetin, and catechins) and their effect on GM composition that leads to improving overall gut health and helping to ameliorate metabolic disorders.     

Community-Based Assessment of Knowledge,Attitude, Practices and Risk Factors Regarding COVID-19 Among Pakistanis Residents During a Recent Outbreak: A Cross-Sectional Survey

Exceptional precautionary measures have been adopted to stop the transmission and control of COVID-19 through the world and Pakistan is facing lockdown in this scenario. Public loyalty to precautionary measures is affected by their knowledge, attitude, risk factors and practices (KAP) towards COVID-19. The present study was conducted among the Pakistani residents to observe the knowledge, attitude, practices and risk factors towards COVID-19 outbreak in Pakistan. A questionnaire was designed, and a cross-sectional survey was conducted among participants of the study area. Participants were asked the questions regarding knowledge, attitude, practices and risk factors towards COVID-19. Data were analyzed by SPSS and t/F test and correlation was applied among the knowledge, attitude, risk factors and practices. A total of 1060 questionnaires were received. 1004 were included while 56 were excluded. The highest representation was from Punjab province (65.6%), female (63%) and age group of 21–30 years (62.1%). Most participants were single (85%), Muslim (99.4%), Urdu speaking (45.6%) and were graduates (51.5%). Most of the participants were students (52.9%) and were from economically middle-class families (40.8%). The knowledge was positively correlated with attitude and practices whereas negatively correlated with risk factors (P?<?0.05). The attitude was negatively correlated with risk factor and positively correlated with practices. The risk factors and practices were positively correlated with each other. Health education program to improve the COVID-19 knowledge, attitude, practices and risk factors should be initiated to combat current health challenge.

     

Biochemical and antitumor activity of trimidox,a new inhibitor of ribonucleotide reductase

Trimidox (3,4,5-trihydroxybenzamidoxime), a newly synthesized analog of didox (N,3,4-trihydroxybenzamide) reduced the activity of ribonucleotide reductase (EC 1.17.4.1) in extracts of L1210 cells by 50% (50% growth-inhibitory concentration, IC₅₀) at 5 M, whereas hydroxyurea, the only ribonucleotide reductase inhibitor in clinical use, exhibited an IC₅₀ of 500 M. Ribonucleotide reductase activity was also measured in situ by incubating L1210 cells for 24 h with trimidox at 7.5 M, a concentration that inhibits cell proliferation by 50% (IC₅₀) or at 100 M for 2 h; these concentrations resulted in a decrease in enzyme activity to 22% and 50% of the control value, respectively. Trimidox and hydroxyurea were cytotoxic to L1210 cells with IC₅₀ values of 7.5 and 50 M, respectively. Versus ribonucleotide reductase, trimidox and hydroxyurea yielded IC₅₀ values of 12 and 87 M, respectively. A dose-dependent increase in life span was observed in mice bearing intraperitoneally transplanted L1210 tumors. Trimidox treatment (200 mg/kg; q1dx9) significantly increased the life span of mice bearing L1210 leukemia (by 82 in male mice and 112% in female mice). The antitumor activity appeared more pronounced in female mice than in male mice. Viewed in concert, these findings suggest that trimidox is a new and potent inhibitor of ribonucleotide reductase and that it is a promising candidate for the chemotherapy of cancer in humans.Abbreviations Didox N,3,4-trihydroxybenzamide - MTT {3-[4,5-dimethyl-thiazo-2yl]}-2,5-diphenyl tetrazolium bromide - PBS phosphate-buffered saline - trimidox 3,4,5-trihydroxybenzamidoxime HCl     

Lead in blood and tissues of mice after administration of low lead doses

Lead levels in whole blood could be determined reliably up to a lower limit of 2 g/100 ml blood, using a modified micromethod of the graphite tube furnace technique. Lead contents of various tissues were also determined by using the automated graphite tube furnace after wet ashing of the organs with nitric acid in autoclaves.Animal experiments with mice showed no measurable increase in blood lead level after a single, 10- or 30-days oral administration of lead in doses of 10–1000 g lead acetate/kg body weight/day. However, these doses led to a rise in tissue lead content. There was a clear dependence of tissue lead content on type of organ examined, lead dose and duration of lead exposure.According to our experiments, the threshold dose which leads to a long-term increase in tissue lead content is assumed to be about 100 g lead acetate/kg body weight/day, orally administered.We are thankful to Prof. Dr. H. Rüssel, Hannover and Dr. M. Fleischer, Saarbrücken for helping in comparison studies.We would also like to thank Mr. H. Dick and Miss. Ch. Hecker for the technical and laboratory assistance.