Identification of Antimycobacterial Natural Products from a Library of Marine Invertebrate Extracts

Tuberculosis (TB) remains a public health crisis, requiring the urgent identification of new anti-mycobacterial drugs. We screened several organic and aqueous marine invertebrate extracts for their in vitro inhibitory activity against the causative organism, Mycobacterium tuberculosis. Here, we report the results obtained for 54 marine invertebrate extracts. The chemical components of two of the extracts were dereplicated, using 1H NMR and HR-LCMS with GNPS molecular networking, and these extracts were further subjected to an activity-guided isolation process to purify the bioactive components. Hyrtios reticulatus yielded heteronemin 1 and Jaspis splendens was found to produce the bengamide class of compounds, of which bengamides P 2 and Q 3 were isolated, while a new derivative, bengamide S 5, was putatively identified and its structure predicted, based on the similarity of its MS/MS fragmentation pattern to those of other bengamides. The isolated bioactive metabolites and semi-pure fractions exhibited M. tuberculosis growth inhibitory activity, in the rang

Antimycobacterial Activity, Synergism, and Mechanism of Action Evaluation of Novel Polycyclic Amines against Mycobacterium tuberculosis

Mycobacterium tuberculosis has developed extensive resistance to numerous antimycobacterial agents used in the treatment of tuberculosis. Insufficient intracellular accumulation of active moieties allows for selective survival of mycobacteria with drug resistance mutations and accordingly promotes the development of microbial drug resistance. Discovery of compounds with new mechanisms of action and physicochemical properties that promote intracellular accumulation, or compounds that act synergistically with other antimycobacterial drugs, has the potential to reduce and prevent further drug resistance. To this end, antimycobacterial activity, mechanism of action, and synergism in combination therapy were investigated for a series of polycyclic amine derivatives. Compound selection was based on the presence of moieties with possible antimycobacterial activity, the inclusion of bulky lipophilic carriers to promote intracellular accumulation, and previously demonstrated bioactivity that potentially support inhibition of efflux pump activity. The most potent antimycobacterial demonstrated a minimum inhibitory concentration (MIC99) of 9.6 μM against Mycobacterium tuberculosis H37Rv. Genotoxicity and inhibition of the cytochrome bc1 respiratory complex were excluded as mechanisms of action for all compounds. Inhibition of cell wall synthesis was identified as a likely mechanism of action for the two most active compounds (14 and 15). Compounds 5 and 6 demonstrated synergistic activity with the known Rv1258c efflux pump substrate, spectinomycin, pointing to possible efflux pump inhibition. For this series, the nature of the side chain, rather than the type of polycyclic carrier, seems to play a determining role in the antimycobacterial activity and cytotoxicity of the compounds. Contrariwise, the nature of the polycyclic carrier, particularly the azapentacycloundecane cage, appears to promote synergistic activity. Results point to the possibility of combining an azapentacycloundecane carrier with a side chain that promotes antimycobacterial activity to develop dual acting molecules for the treatment of Mycobacterium tuberculosis

The effects of the wild african potato (hypoxis hemerocallidea) supplementation on streptozotocin-induced diabetic wistar rats reproductive function

Thesis (MTech (Biomedical Technology))--Cape Peninsula University of Technology, 2015.Diabetes mellitus (DM) has been reported to be one of the greatest global public health threats. Statistics of the fertility status of modern society has linked increased DM to a decrease in fertility rates. Hyperglycaemia is characteristic of DM that results in a disturbance of proteins, lipids and carbohydrate metabolism leading to an increase production of reactive oxygen species (ROS). In the case where ROS overwhelms antioxidant mechanisms, the body goes into state of oxidative stress (OS). OS plays a vital role in the progression of DM which leads to dysfunction and damage of various organs including that of the reproductive system. Os has shown to cause damage to the sperm membraneby oxidation of polyunsaturated fatty acids (PUFA’s) as the sperm membrane are rich in PUFA’s. This damage contributes to reduced sperm motility, concentration, morphological abnormalities and the sperms ability to fuse with the ZP of the oocyte. DM has been observed to cause testicular degeneration by interrupting sertoli cell production and maintenance thus resulting in a disturbance of the normal functioning of the reproductive system. Experimental studies have targeted more natural sources for treating DM and its complications of the reproductive system. Plants and natural dietary substances have shown to have high antioxidant contents that combat DM induced oxidative stress. This study explored the effect the Hypoxis hemerocallidea (H. hemerocallidea) supplementation on testicular and epididymal tissue, sperm motility and reproductive hormones in male wistar rats. The experiment were conducted for 6 weeks and the rats (230-260 grams) were randomly divided into 5 groups (n=12 per group). Diabetes was induced in 3 of the 5 groups. The first group was the normal control group (A), second the diabetic control group (B), third was the diabetic group treated with 800mg/kg H. hemerocallidea (group C), fourth the diabetic group treated with 200mg/kg H. hemerocallidea (group D) and fifth the non-diabetic group supplemented with 800mg/kg H. hemerocallidea (group E). Blood glucose showed a significant increase in the diabetic group when compared to the normal control and treated groups. H. hemerocallidea showed improvement in sperm motility and sperm morphology more at 800mg/kg when compared to diabetic group and diabetic group treated with 200mg/kg. Body, testicular and epipidymal weights of diabetic control were significantly lower when compared to the other groups. Testicular and epididymal Malondialdehyde levels were decreased in normal control, diabetic groups treated with different doses of H. hemerocallidea and the non-diabetic group supplemented with H. hemerocallideaon comparing with the diabetic control group. Antioxidants such as Superoxide dismutase, Catalase and total Glutathione activity was observed to be dosage dependent in certin groups but most showed a significant increase when compared to the diabetic control group. The total antioxidant capacity was measured using Oxygen radical absorbance capacity (ORAC) and Ferric ion reducing antioxidant power (FRAP); increase was observed when normal control group and treated groups were compared to the diabetic group. Testosterone and estradiol levels were also increased when the normal control group and treated groups were compared to the diabetic control group. Based on our findings it can be concluded that H. hemerocallidea supplementation can potentially be used to counteract deleterious effects of DM on the male reproductive system

Chronic disease, allergies, and increased years of running are risk factors predicting gradual onset running-related injuries in ultramarathon runners—SAFER XIX study in 29 585 race entrants

OBJECTIVES : To identify risk factors that predict gradual onset running-related injuries (GORRIs) in ultramarathon runners entering a mass community-based event. DESIGN : Descriptive cross-sectional study. SETTING : Two Oceans 56 km ultramarathon 2012 to 2015. PARTICIPANTS : Race entrants (n = 42 003) completed a compulsory pre-race medical history questionnaire; 29 585 (70.4%) of entrants consented. DEPENDENT/OUTCOME VARIABLE : A history of GORRIs in the past 12 months among race entrants. MAIN OUTCOME MEASURES : In a multi-variate model, runner demographics, training variables (years of recreational running, weekly running distance, training running speed), history of chronic disease (composite score), and history of allergies were included as factors predicting GORRIs. Prevalence (%) and prevalence ratios (PR, 95% CIs) are reported. RESULTS : The lifetime prevalence of GORRIs in ultramarathon runners was 24.4%. Independent factors predicting GORRIs were: higher chronic disease composite score (PR = 2.05 times increase risk for every 2 additional chronic diseases; P < 0.0001), history of allergies (PR = 1.66; P < 0.0001), increased years of recreational running (PR = 1.07 times increased risk for every 5 year increase in running; P < 0.0001), lower average weekly running distance (PR = 0.98 times decreased risk for every 15 km increase weekly running distance; P < 0.0001), and slower average training running speed (PR = 0.96 times decreased risk for every km/h increase in training running speed; P < 0.0001). CONCLUSIONS : Novel risk factors predicting GORRIs are increased number of chronic diseases and a history of allergies. These factors, together with training variables (years of recreational running, weekly running distance, and training running speed) can be targeted to develop and implement injury prevention, treatment, and rehabilitation interventions in ultramarathon runners.IOC Research Centre (South Africa) and South African Medical Research Council.http://www.cjsportmed.com2022-06-09hj2021Sports Medicin

Chronic Disease, Allergies, and Increased Years of Running Are Risk Factors Predicting Gradual Onset Running-Related Injuries in Ultramarathon Runners—SAFER XIX Study in 29 585 Race Entrants

OBJECTIVES : To identify risk factors that predict gradual onset running-related injuries (GORRIs) in ultramarathon runners entering a mass community-based event. DESIGN : Descriptive cross-sectional study. SETTING : Two Oceans 56 km ultramarathon 2012 to 2015. PARTICIPANTS : Race entrants (n = 42 003) completed a compulsory pre-race medical history questionnaire; 29 585 (70.4%) of entrants consented. DEPENDENT/OUTCOME VARIABLE : A history of GORRIs in the past 12 months among race entrants. MAIN OUTCOME MEASURES : In a multi-variate model, runner demographics, training variables (years of recreational running, weekly running distance, training running speed), history of chronic disease (composite score), and history of allergies were included as factors predicting GORRIs. Prevalence (%) and prevalence ratios (PR, 95% CIs) are reported. RESULTS : The lifetime prevalence of GORRIs in ultramarathon runners was 24.4%. Independent factors predicting GORRIs were: higher chronic disease composite score (PR = 2.05 times increase risk for every 2 additional chronic diseases; P < 0.0001), history of allergies (PR = 1.66; P < 0.0001), increased years of recreational running (PR = 1.07 times increased risk for every 5 year increase in running; P < 0.0001), lower average weekly running distance (PR = 0.98 times decreased risk for every 15 km increase weekly running distance; P < 0.0001), and slower average training running speed (PR = 0.96 times decreased risk for every km/h increase in training running speed; P < 0.0001). CONCLUSIONS : Novel risk factors predicting GORRIs are increased number of chronic diseases and a history of allergies. These factors, together with training variables (years of recreational running, weekly running distance, and training running speed) can be targeted to develop and implement injury prevention, treatment, and rehabilitation interventions in ultramarathon runners.IOC Research Centre (South Africa) and South African Medical Research Council.http://www.cjsportmed.com2022-06-09hj2021Sports Medicin

Days until return-to-play differ for sub-categories of acute respiratory tract illness in Super Rugby players : a cross-sectional study over 5 seasons (102,738 player-days)

OBJECTIVES : To document incidence rate and severity of specific sub-categories of respiratory tract illness (RTill) in rugby players during the Super Rugby tournament. DESIGN : Cross-sectional study. METHODS : Team physicians completed daily illness logs in 537 professional male rugby players from South African teams participating in the Super Rugby Union tournaments (2013–2017) (1141 player-seasons, 102,738 player-days). The incidence rate (IR: illness episodes/1000 player-days) and severity [%RTill resulting in time-loss, illness burden (IB: days lost to illness/1000 player-days) and days until return-to-play (DRTP)/single illness (mean: 95% Confidence Intervals)] are reported for the following specific sub-categories of RTill: non-infective respiratory tract illness (RTnon-inf), respiratory tract infections (RTinf), influenza-like illness, infective sinusitis, upper respiratory tract infections (URTinf), lower respiratory tract infections (LRTinf). RESULTS : The overall IR of RTill was 2.9 (2.6–3.3). IR was higher for RTinf (2.5; 2.2–2.9) vs. RTnon-inf (0.4; 0.3–0.6) (p < 0.001). For sub-categories the highest IR was in URTinf (1.9; 1.7–2.2), while the % illness causing time-loss was influenza-like illness (100%), LRTinf (91.7%), infective sinusitis (55.6%), and URTinf (49.0%). IB was highest for URTinf (2.0; 1.6–2.5), and the DRTP/single illness was highest for LRTinf (3.2; 2.3–4.4), and influenza-like illness (2.1; 1.6–2.8). CONCLUSIONS : RTinf accounted for >57% of all illness during the Super Rugby tournament, and mostly URTinf. Influenza-like illness. LRTinf caused time-loss in >90% cases. URTinf, LRTinf and influenza-like illness resulted in the highest burden of illness and LRTinf caused the highest DRTP. Prevention strategies should focus on mitigating the risk of RTinf, specifically URTinf, LRTinf and influenza-like illness.South African Rugby (SA Rugby)http://www.elsevier.com/locate/jsam2022-06-25hj2021Speech-Language Pathology and Audiolog