The Distribution of Interferon-Alpha in Normal Human Tissues

The presence of interferon-alpha (IFN-alpha) in human tissues has been described extensively in viral infections. In the last decade many workers have also shown the presence of low levels of IFN-alpha in conditions other than viral infections. While the precise origin of the synthesis of low levels of IFN-alpha in these physiological conditions has not been clearly defined, some evidence has suggested that macrophages may be involved. In an attempt to find the likely source of IFN-alpha in physiological conditions, an initial study was carried out in which the cellular distribution of immunoreactive IFN-alpha was studied in formalin fixed paraffin embedded normal adult human tissues from 38 different organs using various immunocytochemical techniques. These samples were drawn from over 300 individuals none of whom had evidence of viral infection. Tissue histiocytes from all organs in the body, with the exception of cerebral and cerebellar cortex in brain and renal cortex and medulla, stained positively for IFN-alpha. Kupffer cells, pulmonary alveolar macrophages and lymph node macrophages were also positive for IFN-alpha. Parenchymal cells in some other organs also contained immunoreactive IFN-alpha. These included syncytiotrophoblast in first, second and third trimester placentas, cuboidal lining cells of the choroid plexus in the brain, thyroid follicullar cells, pituitary endocrine cells, adrenocortical cells and parathyroid endocrine cells. These findings are compatible with previous suggestions that IFN-alpha may be synthesized and released in the absence of viral infection and may have a role in normal physiology. The presence of IFN-alpha in most cells of the mononuclear phagocyte system suggests that these cells play a major role in the defence against viral infection. This speculation, however does not preclude other possible roles for IFN-alpha, such as modulation of cell growth, major histocompitability antigen expression etc. The demonstration of immunoreactive IFN-alpha in formalin fixed paraffin embedded normal adult human tissues prompted other studies. In the first of these studies the cellular distribution of immunoreactive IFN-alpha was studied in formalin fixed paraffin embedded normal human autopsy tissues from 32 fetuses (7-42 weeks gestation) and 20 infants (aged from a few hours to 24 months). This study was performed to test the hypothesis that microbes have a role in switching on IFN-alpha synthesis. Fetal tissues are "germ free" while the infants had been exposed to a normal microbial flora. Immunoreactive IFN-alpha was first seen at 9 weeks gestation in macrophages in the fetal liver and thereafter was seen in macrophages in most other organs except in kidneys and cerebral and cerebellar cortex. When infant lungs were compared with fetal lungs a statistically significant increase in the number of macrophages (P< 0.0001, Mann-Whitney test) and the percentage of these cells expressing IFN-alpha (P <0.0005, Mann-Whitney test) was noted in infant lungs. No such changes were observed in spleen, liver and thymus following birth. These findings suggested that there is a basal level of IFN-alpha production by macrophages, which is not dependent on microbial products, but that such microbial products can enhance synthesis of this cytokine. Immunoreactive IFN-alpha was also demonstrated in parenchymal cells of thyroid gland, choroid plexus in brain, anterior pituitary gland and adrenal gland in the fetal and infant tissues. These findings were almost identical to those seen in adult tissues. In a separate study an attempt was made to extract, detect and quantify IFN-alpha in human tissues using protein extraction and an immunoradiometric assay kit for the detection of IFN-alpha. 20 placentas (14-42 weeks gestation) obtained fresh within 1-2 hours of vaginal delivery, 4 specimens of amniotic fluid obtained at the time of caesarean section from 37-39 weeks gestation pregnancies, 10 samples of choroid plexus and cerebral cortex, 11 thyroid glands and 9 fetal adrenal glands from adult and fetal autopsies performed within 10-24 hours of death were studied. IFN-alpha was detected in 9 placentas, 1 adult thyroid gland and all 4 amniotic fluids. However, this study failed to detect IFN-alpha in the remaining placentas and adult thyroid glands and in all choroid plexuses, cerebral cortex and fetal adrenal glands. Formalin fixed paraffin embedded tissues from these organs did show immunoreactive IFN-alpha in cells using the immunocytochemical techniques. Finally an attempt was made to detect IFN-alpha messenger RNA (mRNA) in normal human tissues using an in situ hybridization method

A new route to the synthesis of diarylmethanes by oxidation of 2,3-dimethylphenol with [Fe(DMF)3C12][FeC14]

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Effectiveness of clean intermittent self catheterization in patients with recurrent urethral stricture post visual internal urethrotomy

OBJECTIVE :   Objective of the study is to determine the effectiveness of CISC in management of recurrent urethral strictures after visual internal urethrotomy.  METHODOLOGY :  This study   performed in department of urology   Saidu teaching hospital Swat  from June 2016 to July 2019 on 215 patients who were diagnosed as having urethral stricture disease. Patients were counseled  for CISC after removal of catheter 2 times a day for 8 weeks  and  at 8th  week cystourethroscopy performed along with detail  evaluation of symptoms of urethral stricture to know  recurrence of stricture.  RESULTS:   81.39% patients have no urethral stricture on cystourethroscopy  and symptomatic evaluation at 8th week  post visual internal urethrotomy  while 18.60%  patients have recurrent urethral stricture . Length of urethral stricture is the most important prognostic factor, stricture of less than 1 cm has success rate of 62.39% while stricture of more than one cm length has success rate of 20% as shown in table IV.  CONCLUSION:  In this study it has been confirmed that CISC  is safe ,cost effective procedure and most of the patients can do it in home with out any complications.

Study protocol of DIVERGE, the first genetic epidemiological study of major depressive disorder in Pakistan

INTRODUCTION: Globally, 80% of the burdenof major depressive disorder (MDD) pertains to low- and middle-income countries. Research into genetic and environmental risk factors has the potential to uncover disease mechanisms that may contribute to better diagnosis and treatment of mental illness, yet has so far been largely limited to participants with European ancestry from high-income countries. The DIVERGE study was established to help overcome this gap and investigate genetic and environmental risk factors for MDD in Pakistan. METHODS: DIVERGE aims to enrol 9000 cases and 4000 controls in hospitals across the country. Here, we provide the rationale for DIVERGE, describe the study protocol and characterise the sample using data from the first 500cases. Exploratory data analysis is performed to describe demographics, socioeconomic status, environmental risk factors, family history of mental illness and psychopathology. RESULTS AND DISCUSSION: Many participants had severe depression with 74% of patients who experienced multiple depressive episodes. It was a common practice to seek help for mental health struggles from faith healers and religious leaders. Socioeconomic variables reflected the local context with a large proportion of women not having access to any education and the majority of participants reporting no savings. CONCLUSION: DIVERGE is a carefully designed case-control study of MDD in Pakistan that captures diverse risk factors. As the largest genetic study in Pakistan, DIVERGE helps address the severe underrepresentation of people from South Asian countries in genetic as well as psychiatric research

Study protocol of DIVERGE, the first genetic epidemiological study of major depressive disorder in Pakistan.

INTRODUCTION: Globally, 80% of the burdenof major depressive disorder (MDD) pertains to low- and middle-income countries. Research into genetic and environmental risk factors has the potential to uncover disease mechanisms that may contribute to better diagnosis and treatment of mental illness, yet has so far been largely limited to participants with European ancestry from high-income countries. The DIVERGE study was established to help overcome this gap and investigate genetic and environmental risk factors for MDD in Pakistan. METHODS: DIVERGE aims to enrol 9000 cases and 4000 controls in hospitals across the country. Here, we provide the rationale for DIVERGE, describe the study protocol and characterise the sample using data from the first 500 cases. Exploratory data analysis is performed to describe demographics, socioeconomic status, environmental risk factors, family history of mental illness and psychopathology. RESULTS AND DISCUSSION: Many participants had severe depression with 74% of patients who experienced multiple depressive episodes. It was a common practice to seek help for mental health struggles from faith healers and religious leaders. Socioeconomic variables reflected the local context with a large proportion of women not having access to any education and the majority of participants reporting no savings. CONCLUSION: DIVERGE is a carefully designed case-control study of MDD in Pakistan that captures diverse risk factors. As the largest genetic study in Pakistan, DIVERGE helps address the severe underrepresentation of people from South Asian countries in genetic as well as psychiatric research

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

Antifilarial activity of the extract of leaves of Mimusops elengi Linn. on Setaria cervi in vitro

Effect of aqueous and alcoholic extracts of the leaves of Mimusops elengi Linn. on the spontaneous movements of both the whole worm, the split preparation of Setaria cervi and on the survival of microfilariae in vitro was studied. Alcoholic extract of leaves caused inhibition of the spontaneous movements of the whole worm and the split preparation of S. cervi, while aqueous extract did not show any effect. The initial stimulatory effect was not observed by alcoholic extract of leaves on the spontaneous movements of whole worm as well as split preparation. The concentrations required to inhibit the movements of the whole worm and split preparation for alcoholic extract of leaves were 280 and 40 mg/ml, respectively, suggesting a cuticular permeability barrier. Alcoholic extract of leaves caused death of microfilariae in vitro. LC50 and LC90 were 15 and 25 ng/ml, respectively for alcoholic extract of leaves

Phytochemical and pharmacological investigations of Egyptian clover, Trifolium alexandrinum L.

In continuation of our studies on the phytoconstituents of the Trifolium species (Fabaceae-Trifolieae), mostly occurring in India and other parts of the world, we have examined Trifolium alexandrinum L., which is also known as Barseem or Egyptian clover. Its aerial part is used as hay or pasture and seeds are used as an antidiabetic. Phytochemical data, obtained with several Trifolium species previously investigated, allowed the characterization of many secondary metabolites mainly consisting of flavonoids and aliphatic compounds structural types. The aim was to identify and characterize phenolic components in the leaves of T. alexandrinum for antimicrobial and antioxidant activities. Eight different flavonoids were detected after multistep chromatographic fractionation and preparative TLC using different solvent systems. The isolated flavonoids after purification from ethyl acetate extract were identified as 1) 5,7-dihydroxy-4'-O-methyl isoflavone, 2) 5,7,4'trihydroxy isoflavone, 3) 5,7,4'-trihydroxy flavone, 4) 5,7,3',4'-tetrahydroxy flavone, 5) apigenin 7-0-β-D-galactopyranoside, and 6) luteolin 7-0-β-glucoside by UV, IR, MS, IH-NMR, 13C-NMR analyses, direct comparison with their authentic samples and different chemical methods. Occurrence of monoflavonoids 3,4,5,6 from this plant is being reported for the first time. Further studies are still in progress to elucidate the structure of the remaining two phenolic compounds. The inhibitory potencies and capacities of different extracts against many gram positive and gram negative bacteria were also tested