Diarrhea after kidney transplantation: A study of risk factors and outcomes.

Background: Diarrhea in kidney transplant recipients (KTRs) can be associated with significant morbidity. Material and Methods: We evaluated 198 KTRs for a history of diarrhea post-kidney transplant at a tertiary care center in western India over 1 year. A protocol-based evaluation of diarrhea was done with respect to clinical features, diagnostic evaluation, associated acute allograft dysfunction, and its impact on long-term allograft function. Primary outcomes of interest were: chronic allograft injury (CAI) and the need for mycophenolate mofetil (MMF) withdrawal. We also assessed the effect of MMF withdrawal on the risk of the development of CAI. Results: Eighty-five of 198 (42.5%) recipients experienced diarrhea and a total of 140 diarrheal episodes were evaluated. The mean age of these 85 recipients was 38 ± 12 years and 72 (84.7%) were males. 73 of 85 recipients were on MMF at the time of diarrhea and in 35 (48%) of them MMF withdrawal was needed for chronic and persistent symptoms. Diarrhea was attributed to infective etiologies in 90 of 140 (64.2%) cases. Among the microbiologically confirmed infective diarrheal episodes, giardia and cryptosporidium were the common pathogens in 11/28 (39%) and 6/28 (21.4%) episodes respectively. One hundred and twenty-eight episodes out of 140 (91.4%) episodes were complicated by acute allograft dysfunction. Forty-one of 85 recipients (48.2%) developed chronic allograft injury and 12 (14.1%) developed allograft rejection (acute and/or chronic). Probability of chronic allograft injury was higher in those with MMF withdrawal. Conclusion: Diarrhea post-kidney transplant adversely affects graft function, especially after MMF withdrawal.

Ponatinib Inducing a Panuveitis with Choroidal Effusions and Neurosensory Retinal Detachment in a Patient with Chronic Myeloid Leukaemia.

CASE SUMMARY: We present the case of a 50 year old male patient being treated for chronic myeloid leukemia by the tyrosine kinase inhibitor, Ponatinib. After 3 months of treatment, he developed a sight-threatening granulomatous panuveitis in both eyes, with choroidal effusions and neurosensory retinal detachments. Except for a positive interferon-gamma release assay suggesting previous Tuberculosis exposure, all uveitis investigations were normal. Discontinuation of the suspected causative drug led to resolution of signs and a consequent improvement in visual acuity. CONCLUSION: Ponatinib use may be associated with with a uveitic phenotype that is reminiscent of Harada's disease. We compare and contrast this rare ocular phenomenon with Vogt-Koyanagi-Harada syndrome and discuss a possible immunological basis.

Female genital tuberculosis in light of newer laboratory tests: A narrative review.

Female genital tract tuberculosis (FGTB) is a chronic disease with varied presentation. The diagnosis of FGTB for early institution of treatment remains a clinical challenge. Its laboratory diagnosis is difficult because of paucibacillary nature of the condition and limitation of available diagnostic tests. In view of the intricate problems in diagnosis of FGTB, physicians tend to over treat with empirical anti-tuberculosis drugs. Apart from concerns of drug toxicity, this may be a contributing factor in the increasing incidence of multidrug-resistant TB reported in India. The main goal for advances in TB diagnostics is to reduce delay in diagnosis and treatment. In addition, there should be reduced complexity, improving robustness, and improving accuracy of the laboratory test for diagnosis of Female genital tuberculosis. OBJECTIVE: This narrative review is written with the following objectives. 1) To get a comprehensive overview as well as recent advances in diagnostic test used in the detection of FGTB. 2) To understand the limitations as well as advantages of these laboratory diagnostic test. 3) To provide clinical guidance regarding the detection in susceptible women. METHOD: The literature search was performed using electronic database of Pubmed, Medline, Embase and Google Scholar. Grey literature search was also done. Studies published in English were included. Following keywords were used for search - Tuberculosis, extra pulmonary tuberculosis, female genital tuberculosis, diagnosis of female genital tract tuberculosis. The personal knowledge and experience of authors in the field, helped in archiving the relevant articles. RESULT: Studies suggest that though culture is an invaluable contributor in the diagnosis of FGTB, molecular tests like PCR, LAMP, Xpert MTB/RIF and line probe assays have shown potential and are now being explored to strengthen the diagnostic algorithm of FGTB. CONCLUSION: The use of algorithm approach with combination of both rapid culture and newer molecular techniques will facilitate the accurate and timely diagnosis of FGTB.

Health-care waste management in India.

Health-care waste management in India is receiving greater attention due to recent regulations (the Biomedical Wastes (Management & Handling) Rules, 1998). The prevailing situation is analysed covering various issues like quantities and proportion of different constituents of wastes, handling, treatment and disposal methods in various health-care units (HCUs). The waste generation rate ranges between 0.5 and 2.0 kg bed-1 day-1. It is estimated that annually about 0.33 million tonnes of waste are generated in India. The solid waste from the hospitals consists of bandages, linen and other infectious waste (30-35%), plastics (7-10%), disposable syringes (0.3-0.5%), glass (3-5%) and other general wastes including food (40-45%). In general, the wastes are collected in a mixed form, transported and disposed of along with municipal solid wastes. At many places, authorities are failing to install appropriate systems for a variety of reasons, such as non-availability of appropriate technologies, inadequate financial resources and absence of professional training on waste management. Hazards associated with health-care waste management and shortcomings in the existing system are identified. The rules for management and handling of biomedical wastes are summarised, giving the categories of different wastes, suggested storage containers including colour-coding and treatment options. Existing and proposed systems of health-care waste management are described. A waste-management plan for health-care establishments is also proposed, which includes institutional arrangements, appropriate technologies, operational plans, financial management and the drawing up of appropriate staff training programmes.

Three new pseudodistomins, piperidine alkaloids from the ascidian Pseudodistoma megalarva.

Bioassay-guided fractionation of the MeOH-CH2Cl2 extract of the Micronesian ascidian Pseudodistoma megalarva yielded three new piperidine alkaloids, pseudodistomins D-F (3-5) and the previously reported pseudodistomins B and C (1 and 2). The structure and stereochemistry of these compounds were established by interpretation of spectral data. Pseudodistomins B-F were found to be active in a cell-based assay for DNA damage induction, but the activity was due to an alternative mechanism.

Two new nitrogenous sesquiterpenes from the sponge Axinyssa aplysinoides.

Bioassay-guided fractionation of the EtOAc extract of the Palauan sponge Axinyssa aplysinoides yielded two novel alkaloids, 1 and 2. The structure of 2-(formylamino)trachyopsane (1) was determined by X-ray analysis; and the structure of N-phenethyl-N'-2-trachyopsanylurea (2), by interpretation of the spectral data.

Daleformis, a new phytoalexin from the roots fo Dalea filiciformis: an inhibitor of endothelin converting enzyme.

As part of a search for novel inhibitors of endothelin converting enzyme (ECE), the MeOH-CH2Cl2 extract of the roots of Dalea filiciformis was shown to be active. Bioassay-guided fractionation of the extract yielded a novel phytoalexin, daleformis (1), whose structure was determined by interpretation of spectral data and X-ray analysis. Daleformis (1) inhibited ECE with an IC50 of 9 microM.

Rigidone, a sesquiterpene o-quinone from the gorgonian Pseudopterogorgia rigida.

As part of a search for novel biologically active compounds in the Macrophage Scavenger Receptor (MSR) assay, the EtOAc extract of a gorgonian coral, Pseudopterogorgia rigida, was shown to be active. Bioassay-guided fractionation of the extract yielded curcuphenol, curcuhydroquinone, curcuquinone, and a novel o-quinone, rigidone (1). The structure and stereochemistry of 1 was determined by interpretation of spectral data and chemical transformation.

Halistanol disulfate B, a novel sulfated sterol from the sponge Pachastrella sp.: inhibitor of endothelin converting enzyme.

As part of a search for novel inhibitors of endothelin converting enzyme (ECE), the MeOH extract of a South African sponge, Pachastrella sp., was shown to be active. Bioassay-guided fractionation of the extract yielded a novel sterol sulfate, halistanol disulfate B (1). The structure and stereochemistry of 1 was established mainly by interpretation of spectral data. Disulfate (1) was found to be active at a micromolar concentration in the ECE assay.

Plakortides, novel cyclic peroxides from the sponge Plakortis halichondrioides: activators of cardiac SR-CA(2+)-pumping ATPase.

As part of a search for novel activators of Ca2+ pumping activity of cardiac SR- (sarcoplasmic reticulum), the EtOAc extract of the Jamaican sponge Plakortis halichondrioides was shown to be active. Bioassay-guided fractionation of the extract followed by preparative TLC and HPLC yielded several known and novel compounds. Three of the novel cyclic peroxides, plakortides F, G, and H (3, 4, and 5) are the subject of this report. Their structures including relative stereochemistry were established by interpretation of spectral data. Micromolar concentrations of plakortides F-H (3-5) were found to significantly enhance Ca2+ uptake by SR.

Kinetic and mutational analysis of human immunodeficiency virus type 1 reverse transcriptase inhibition by inophyllums, a novel class of non-nucleoside inhibitors.

Inophyllums are novel non-nucleoside inhibitors of human immunodeficiency virus (HIV) type 1 reverse transcriptase identified through an enzyme screening program and isolated from the plant Calophyllum inophyllum. The kinetics of reverse transcriptase inhibition by inophyllum B were characterized using recombinant purified enzyme, a heteropolymeric RNA template, and a scintillation proximity assay. Preincubation of inhibitor with the enzyme-template-primer complex for 11 min was required for maximal inhibition of reverse transcriptase to occur, suggesting that inophyllum B had a slow on-rate and that template-primer must bind to reverse transcriptase prior to inhibitor binding. Inhibition of reverse transcriptase by inophyllums was shown to be reversible. When thymidine triphosphate was the variable substrate, inophyllum B inhibited reverse transcriptase noncompetitively with a Ki of 42 nM. Enzyme inhibition with respect to template-primer was uncompetitive with a Ki of 26 nM. Reverse transcriptase enzymes containing point mutations in which tyrosine 181 was changed to either cysteine or isoleucine exhibited marginal resistance to inophyllums but were resistant to (+)-(5S)-4,5,6,7-tetrahydro-9-chloro-5-methyl-6- (3-methyl-2-butenyl)-imidazo[4,5,1-j,k][1,4]benzodiazepin-2-(1H)-t hione (TIBO R82913). A mutant enzyme in which tyrosine 188 was changed to leucine was cross-resistant to both inophyllum B and TIBO R82913, as was HIV type 2 reverse transcriptase. These studies suggest that inophyllum B and TIBO R82913 bind to distinct but overlapping sites. Inhibition of avian myeloblastosis virus reverse transcriptase and Moloney murine leukemia virus reverse transcriptase by inophyllum B was detectible, suggesting that these inhibitors may be more promiscuous than other previously described non-nucleoside inhibitors. Inophyllums were active against HIV type 1 in cell culture with IC50 values of approximately 1.5 microM. These studies imply that the inophyllums have a novel mechanism of interaction with reverse transcriptase and as such could conceivably play a role in combination therapy.

The inophyllums, novel inhibitors of HIV-1 reverse transcriptase isolated from the Malaysian tree, Calophyllum inophyllum Linn.

As part of a search for novel inhibitors of HIV-1 reverse transcriptase, the acetone extract of the giant African snail, Achatina fulica, was shown to be active. Fractionation of the extract yielded inophyllums A, B, C, and E and calophyllolide (1a, 2a, 3a, 3b, and 6), previously isolated from Calophyllum inophyllum Linn., a known source of nutrition for A. fulica. From a methanol/methylene chloride extract of C. inophyllum, the same natural products in considerably greater yield were isolated in addition to a novel enantiomer of soulattrolide (4), inophyllum P (2b), and two other novel compounds, inophyllums G-1 (7) and G-2 (8). The absolute stereochemistry of inophyllum A (1a) was determined to be 10(R), 11(S), 12(S) from a single-crystal X-ray analysis of its 4-bromobenzoate derivative, and the relative stereochemistries of the other inophyllums isolated from C. inophyllum were established by a comparison of their 1H NMR NOE values and coupling constants to those of inophyllum A (1a). Inophyllums B and P (2a and 2b) inhibited HIV reverse transcriptase with IC50 values of 38 and 130 nM, respectively, and both were active against HIV-1 in cell culture (IC50 of 1.4 and 1.6 microM). Closely related inophyllums A, C, D, and E, including calophyllic acids, were significantly less active or totally inactive, indicating certain structural requirements in the chromanol ring. Altogether, 11 compounds of the inophyllum class were isolated from C. inophyllum and are described together with the SAR of these novel anti-HIV compounds.

A screen for inhibitors of DNA recombination: identification of two new spirostanol glycosides from Chamaedorea linearis.

Two new glycosides have been isolated from the MeOH extract of the stem wood and stem bark of an Ecuadorian plant Chamaedorea linearis, and their structures have been determined by spectroscopic means and X-ray analysis of the aglycone to be 1-O-[beta-L-fucopyranosyl-(4'-sulfate)]-25R,5 alpha-spirostane-1 beta, 3 beta-diol [1]) and 1-O-[beta-L-fucopyranosyl-(4'-sulfate)]-25R,5 alpha-spirostane-1 alpha, 3 beta-diol [2]. These compounds were identified in a screen for inhibitors of recombinational DNA repair. Cytotoxic activity was also demonstrated.

A diterpene epoxide from the marine brown alga Dictyota sp.: possible vasopressin V1 receptor antagonist.

A novel epoxide, in addition to eight known diterpenes, has been isolated from a marine brown alga of the genus Dictyota. The structures of these compounds were established by the interpretation and comparison of spectral data with literature data. Most of the isolates demonstrated vasopressin receptor antagonist activity in vitro with the new epoxide being the most active of the diterpenes tested.

Brominated polyacetylenic acids from the marine sponge Xestospongia muta: inhibitors of HIV protease.

The EtOAc extract of the sponge Xestospongia muta collected in Colombus Island, Bahamas, yielded eleven straight-chain unsaturated, polyacetylenic, brominated acids, seven of which were identified on the basis of spectral data, including the unknown acids 2-7. These acetylenic acids are the first known examples that have been shown to inhibit HIV protease, a critical enzyme in the replication of human immunodeficiency virus.

Antibacterial constituents of the diatom Navicula delognei.

The novel ester (E)-phytol (5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate++ + (1); (6Z,9Z,12Z,15Z)-hexadecatetraenoic acid; (6Z,9Z,12Z,15Z)-octadecatetraenoic acid; and (6Z,9Z,12Z)-hexadecatrienoic acid isolated from the diatom Navicula delognei f. elliptica, show significant antibacterial activity against Staphylococcus aureus, Staphylococcus epidermidis, Salmonella typhimurium, and Proteus vulgaris. beta-Carotene, alpha-cryptoxanthin, fucoxanthin, lutein, trans-phytol, and plastoquinone-9 were also isolated from this diatom.

A novel sterol peroxide from the sea anenome Metridium senile.

Nine 5 alpha, 8 alpha-epidioxy delta 6 and delta 6,9(11) sterols were identified including the hitherto unknown (22E)-5,8-epidioxy-5 alpha, 8 alpha-stigmasta-6,9(11),22-trien-3 beta-ol 9 from the sea anenome Metridium senile based on 200 MHz 1Hnmr and mass spectral data.