■ Abstract Apoptosis is a genetically programmed, morphologically distinct form of cell death that can be triggered by a variety of physiological and pathological stimuli. Studies performed over the past 10 years have demonstrated that proteases play critical roles in initiation and execution of this process. The caspases, a family of cysteine-dependent aspartate-directed proteases, are prominent among the death proteases. Caspases are synthesized as relatively inactive zymogens that become activated by scaffold-mediated transactivation or by cleavage via upstream proteases in an intracellular cascade. Regulation of caspase activation and activity occurs at several different levels: ( a) Zymogen gene transcription is regulated; ( b) antiapoptotic members of the Bcl-2 family and other cellular polypeptides block proximity-induced activation of certain procaspases; and ( c) certain cellular inhibitor of apoptosis proteins (cIAPs) can bind to and inhibit active caspases. Once activated, caspases cleave a variety of intracellular polypeptides, including major structural elements of the cytoplasm and nucleus, components of the DNA repair machinery, and a number of protein kinases. Collectively, these scissions disrupt survival pathways and disassemble important architectural components of the cell, contributing to the stereotypic morphological and biochemical changes that characterize apoptotic cell death.

Mammalian caspases: structure ,a ctivation ,s ubstrates, and functions during apoptosis

https://research-information.bris.ac.uk/files/134652082/injecting.pdf

Global prevalence of injecting drug use and sociodemographic characteristics and prevalence of HIV, HBV, and HCV in people who inject drugs: a multistage systematic review

The pride in British medicine that was established by this flagship-the first edition of the Oxford textbook of medicine-is rekindled by the second edition. Some rearrangement and expansion of sections have occurred. The first edition indicated that the book was intended for anyone studying or practising clinical medicine (as a first reference source for general practitioners and specialists) and this new edition amply fulfils that challenge. A section on primary care brings this discipline into its rightful place in such a textbook and helps to break down any artificial barrier that may exist between hospital and family practice medicine. One looks for updating between the two editions and apart from increase in size there are 'improvements' throughout-almost completely new and recent references in the section on pituitary and hypothalmic disorders, an account of CT scanning in pituitary and adrenal disease, developments such as magnetic resonance imaging included in the cardiovascular disease section. The section on respiratory disease has illuminating descriptions of the pathophysiology of the airways and gas exchange. The clinical section on asthma is updated to modern concepts. Rheumatology and connective tissue disorders is expanded from eight to 15 subsections. AIDS, dealt with in only three pages, may (one hopes) be in the end a true perspective or, alternatively, this field is changing so rapidly that we can await a major assessment of this condition in a third edition.

Oxford textbook of medicine

Purpose of Review: Microsporidia have emerged as causes of opportunistic infections associated with diarrhea and wasting in AIDS patients. This review describes recent reports of microsporidiosis in HIV-infected individuals and the growing awareness of microsporidiosis in non-HIV-infected populations. Recent Findings: Microsporidia were only rarely recognized as causes of disease in humans until the AIDS pandemic. Implementation of combination antiretroviral therapy (cART) to curtail HIV replication and restore immune status drastically reduced the occurrence of opportunistic infections including those due to microsporidia in HIV-infected individuals. In developing countries where cART is not always accessible microsporidiosis continues to be problematic. Improvement of diagnostic methods over the previous 25 years led to identification of several new species of microsporidia many of which disseminate from enteric to systemic sites of infection and contribute to some unexpected lesions. Among non-HIV-infected but immune-suppressed individuals microsporidia have infected organ transplant recipients children the elderly and patients with malignant disease and diabetes. In otherwise healthy immune-competent HIV seronegative populations self-limiting diarrhea occurred in travelers and as a result of a foodborne outbreak associated with contaminated cucumbers. Keratitis due to microsporidiosis has become problematic and a recent longitudinal evaluation demonstrated that non-HIV-infected individuals seropositive for microsporidia who had no clinical signs continued to intermittently shed organisms in feces and urine. Summary: Greater awareness and implementation of better diagnostic methods are demonstrating that microsporidia contribute to a wide range of clinical syndromes in HIV-infected and non-HIV-infected people. As such microsporidia should be considered in differential diagnoses if no other cause can be defined.

/pdf/microsporidiosis-not-just-in-aids-patients-27qeweade4.pdf

Microsporidiosis: Not just in AIDS patients

Eurycoma longifolia Jack (known as tongkat ali), a popular traditional herbal medicine, is a flowering plant of the family Simaroubaceae, native to Indonesia, Malaysia, Vietnam and also Cambodia, Myanmar, Laos and Thailand. E. longifolia, is one of the well-known folk medicines for aphrodisiac effects as well as intermittent fever (malaria) in Asia. Decoctions of E. longifolia leaves are used for washing itches, while its fruits are used in curing dysentery. Its bark is mostly used as a vermifuge, while the taproots are used to treat high blood pressure, and the root bark is used for the treatment of diarrhea and fever. Mostly, the roots extract of E. longifolia are used as folk medicine for sexual dysfunction, aging, malaria, cancer, diabetes, anxiety, aches, constipation, exercise recovery, fever, increased energy, increased strength, leukemia, osteoporosis, stress, syphilis and glandular swelling. The roots are also used as an aphrodisiac, antibiotic, appetite stimulant and health supplement. The plant is reported to be rich in various classes of bioactive compounds such as quassinoids, canthin-6-one alkaloids, β-carboline alkaloids, triterpene tirucallane type, squalene derivatives and biphenyl neolignan, eurycolactone, laurycolactone, and eurycomalactone, and bioactive steroids. Among these phytoconstituents, quassinoids account for a major portion of the E. longifolia root phytochemicals. An acute toxicity study has found that the oral Lethal Dose 50 (LD50) of the alcoholic extract of E. longifolia in mice is between 1500–2000 mg/kg, while the oral LD50 of the aqueous extract form is more than 3000 mg/kg. Liver and renal function tests showed no adverse changes at normal daily dose and chronic use of E. longifolia. Based on established literature on health benefits of E. longifolia, it is important to focus attention on its more active constituents and the constituents’ identification, determination, further development and most importantly, the standardization. Besides the available data, more evidence is required regarding its therapeutic efficacy and safety, so it can be considered a rich herbal source of new drug candidates. It is very important to conserve this valuable medicinal plant for the health benefit of future generations.

https://www.mdpi.com/1420-3049/21/3/331/pdf

Review on a Traditional Herbal Medicine, Eurycoma longifolia Jack (Tongkat Ali): Its Traditional Uses, Chemistry, Evidence-Based Pharmacology and Toxicology.

Background
One of the largest cross-sectional study in recent years was carried out to investigate the prevalence of intestinal parasitic infections among urban and rural school children from five states namely Selangor, Perak, Pahang, Kedah and Johor in Peninsula Malaysia. This information would be vital for school authorities to influence strategies for providing better health especially in terms of reducing intestinal parasitism.

/pdf/predominance-of-blastocystis-sp-infection-among-school-3277igw19l.pdf

Predominance of Blastocystis sp. Infection among School Children in Peninsular Malaysia.

Microsporidia are considered opportunistic pathogens as evidenced by the significant detection in immunocompromised HIV/AIDS population. Cancer patients receiving chemotherapy are considered to be immunosuppressed. Stool samples were collected from 311 cancer patients in the Klang Valley. Each sample underwent water–ether concentration and staining with modified trichrome stain. Sixty-eight samples were positive by oil immersion examination. Polymerase chain reaction amplification with specific primers on those samples amplified Encephalitozoon intestinalis from two of the samples and Encephalitozoon hellem from one sample.

Incidence of microsporidia in cancer patients.

a b s t r a c t The HIV-positive population, due to their immuno-compromised nature, is considered more susceptible to parasitic infections than other populations. However despite the reports of other opportunistic pathogens such as Cryptosporidium and tuberculosis reported in vulnerable communities, microsporidia have not been highlighted in the local HIV-positive population in Malaysia. This study aimed to provide preliminary information on the prevalence of microsporidia in the local HIV-population. Microsporidia were detected in 21/247 (8.5%) stool samples from the HIV-infected individuals, a significantly higher (P-value <0.05) prevalence than in the control group, in which 5/173 (2.9%) were positive. HIV patients were 3x more at risk for acquiring microspordium (OR: 3.12; 95% CI 1.15–8.44). Spores were ellipsoid in shape with outlines that stained dark pink with the interior a lighter shade. Approximately 21% of the positive specimens were from individuals in the 40–49 years age group. Ten individuals who were positive for microsporidia were also positive for other enteric parasites such as Blastocystis hominis and Giardia lamblia. We detected Encephalitozoon intestinalis DNA following nested PCR from three of 10 samples analysed, as demonstrated by an amplicon of 370 bp. From the findings reported, it appears that microsporidial infection in humans may actually be more common than reported. We strongly advocate greater emphasis on personal hygiene through public education on personal hygiene and the consumption of boiled or filtered water.

Detection of microsporidia in local HIV-positive population in Malaysia.

In the local Malaysian context, herbal plants such as Eurycoma longifolia (Tongkat Ali), Orthosiphon stamineus (MisaiKucing), Ficus deltoidea (Mas Cotek), Zingiber officinale (Halia Bara) and Barringtonia racemosa (Putat) are known and widely used for its therapeutic properties. The first part of this study aims to screen for the anti-protozoal activity of these herbal plant extracts against Blastocystis sp. isolate subtype (ST) 3. Herbal extract with the highest efficacy was further fractionized into water and ethyl acetate fractions and tested against ST1, ST3 and ST5 Blastocystis sp. isolates. These isolates were also exposed to allopathic drugs, Metronidazole (MTZ), Tinidazole, Trimethoprim-sulfamethoxazole(TMP-SMX), Ketoconazole and Nitazoxanide for comparison purpose. Blastocystis sp. isolates from human-derived stool samples were exposed to herbal extracts and allopathic drugs at a concentration of 0.1 mg/ml and 1.0 mg/ml and were incubated at 37 °C. Growth profile studies were carried out. After 72 h of treatment, the viability of Blastocystis sp. as a result of the effects of the drugs and herbal extracts were assessed. Based on the screening process, amongst all the extracts, Tongkat Ali exhibited the highest anti-protozoal activity at 1.0 mg/ml. Between the water and ethyl acetate fractions of Tongkat Ali, the ethyl acetate fraction exhibited a slightly higher percentage of anti-protozoal activity at 1.0 mg/ml across subtypes, ST1 (94.9 %), ST3 (95.1 %) and ST5 (94.3 %). When tested with allopathic drugs, at the same concentration, MTZ exhibited the highest anti-protozoal activity across subtypes, ST1 (95.8 %), ST3 (93.4 %) and ST5 (90.8 %). This study is the first to describe the anti-protozoal properties of Tongkat Ali against Blastocystis sp. isolates. Ethyl acetate fraction of Tongkat Ali demonstrated the highest anti-protozoal activity against Blastocystis sp. isolates and showed a sizeable reduction in the cell count which was comparable with MTZ. Tongkat Ali also demonstrated a more uniformed sensitivity across subtypes in comparison to the allopathic drugs.

/pdf/tongkat-ali-eurycoma-longifolia-a-possible-therapeutic-5bevmnaj9w.pdf

Tongkat Ali (Eurycoma longifolia): a possible therapeutic candidate against Blastocystis sp

People who inject drugs (PWID) in India are at high risk for HIV, with women being at elevated risk. Using a socio-ecological framework, this study assessed whether factors associated with HIV transmission risk behaviors differed across men and women PWID. Data for this cross-sectional study were collected from 6449 PWID in 7 cities in Northeast India. Men (n = 5653) and women (n = 796) PWID were recruited using respondent-driven sampling (RDS). We assessed sex differences in two recent HIV transmission risk behaviors: multiple sex partners and needle/syringe sharing. We used multi-level logistic regression models, which incorporated sampling weights and random intercepts for city, to assess factors associated with these HIV risks, separately among men and women. The prevalence of HIV was significantly higher among women than men (53% vs 18.4%, p<0.01). Nearly 13% of men and 8% of women (p = .30) had multiple partners. Employment in men and relationship status and stigma in women were significantly associated with multiple partners. Approximately 25% of men and 19% of women engaged in needle sharing (p = .16). Younger age in women and depression symptoms in men were significantly associated with increased risk for sharing needles. We found that sexual and drug related risk behaviors were common among PWID in Northeast India, and there were differences between men and women in the socio-ecologic correlates of these behaviors. Contextually-integrated and gender-specific HIV prevention and intervention efforts are needed that consider factors at individual, interpersonal- and community-levels that uniquely impact HIV risks among PWID.

/pdf/gender-differences-in-factors-related-to-hiv-risk-behaviors-jcwjvivsb1.pdf

Gender Differences in Factors Related to HIV Risk Behaviors among People Who Inject Drugs in North-East India.

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