Diabetes Mellitus and Alzheimer's Disease: Understanding Disease Mechanisms, their Correlation, and Promising Dual Activity of Selected Herbs.

ETHNOPHARMACOLOGICAL RELEVANCE: This review explores the link between Type 2 Diabetes Mellitus (T2DM) and diabetes-induced Alzheimer's disease (AD). It emphasizes the shared pathophysiological links and mechanisms between the two conditions, focusing on reduced insulin levels and receptors, impaired glucose metabolism, insulin resistance, mitochondrial dysfunction, and oxidative damage in AD-affected brains-paralleling aspects of T2DM. The review suggests AD as a "diabetes of the brain," supported by cognitive enhancement through antidiabetic interventions. It focuses on the traditionally used Indian herbs as a means to manage both conditions with minimal side effects and toxicity while addressing developmental challenges. AIM OF THE STUDY: This study explores the DM-AD connection, reviewing medicinal herbs with protective potential for both ailments, considering traditional uses and developmental challenges. MATERIALS AND METHODS: Studied research, reviews, and ethnobotanical and scientific data from electronic databases and traditional books. RESULTS: The study analyzes the pathophysiological links between DM and AD, emphasizing their interconnected factors. Eight Ayurvedic plants with dual protective effects against T2DM and AD are thoroughly reviewed with preclinical/clinical evidence. Historical context, phytoconstituents, and traditional applications are explored. Innovative formulations using these plants are examined. Challenges stemming from phytoconstituents' physicochemical properties are highlighted, prompting novel formulation development, including nanotechnology-based delivery systems. The study uncovers obstacles in formulating treatments for these diseases. CONCLUSION: The review showcases the dual potential of chosen medicinal herbs against both diseases, along with their traditional applications, endorsing their use. It addresses formulation obstacles, proposing innovative delivery technologies for herbal therapies, while acknowledging their constraints. The review suggests the need for heightened investment and research in this area.

Comprehensive insights into rheumatoid arthritis: Pathophysiology, current therapies and herbal alternatives for effective disease management.

Rheumatoid arthritis is a chronic autoimmune inflammatory disease characterized by immune response overexpression, causing pain and swelling in the synovial joints. This condition is caused by auto-reactive antibodies that attack self-antigens due to their incapacity to distinguish between self and foreign molecules. Dysregulated activity within numerous signalling and immunological pathways supports the disease's development and progression, elevating its complexity. While current treatments provide some alleviation, their effectiveness is accompanied by a variety of adverse effects that are inherent in conventional medications. As a result, there is a deep-rooted necessity to investigate alternate therapeutic strategies capable of neutralizing these disadvantages. Medicinal herbs display a variety of potent bioactive phytochemicals that are effective in the complementary management of disease, thus generating an enormous potency for the researchers to delve deep into the development of novel phytomedicine against autoimmune diseases, although additional evidence and understanding are required in terms of their efficacy and pharmacodynamic mechanisms. This literature-based review highlights the dysregulation of immune tolerance in rheumatoid arthritis, analyses the pathophysiology, elucidates relevant signalling pathways involved, evaluates present and future therapy options and underscores the therapeutic attributes of a diverse array of medicinal herbs in addressing this severe disease.

Defining the Middle Corona.

The middle corona, the region roughly spanning heliocentric distances from 1.5 to 6 solar radii, encompasses almost all of the influential physical transitions and processes that govern the behavior of coronal outflow into the heliosphere. The solar wind, eruptions, and flows pass through the region, and they are shaped by it. Importantly, the region also modulates inflow from above that can drive dynamic changes at lower heights in the inner corona. Consequently, the middle corona is essential for comprehensively connecting the corona to the heliosphere and for developing corresponding global models. Nonetheless, because it is challenging to observe, the region has been poorly studied by both major solar remote-sensing and in-situ missions and instruments, extending back to the Solar and Heliospheric Observatory (SOHO) era. Thanks to recent advances in instrumentation, observational processing techniques, and a realization of the importance of the region, interest in the middle corona has increased. Although the region cannot be intrinsically separated from other regions of the solar atmosphere, there has emerged a need to define the region in terms of its location and extension in the solar atmosphere, its composition, the physical transitions that it covers, and the underlying physics believed to shape the region. This article aims to define the middle corona, its physical characteristics, and give an overview of the processes that occur there.

A novel UPLC-MS/MS method for simultaneous quantification of trigonelline, 4-hydroxyisoleucine, and diosgenin from Trigonella foenum-graecum extract: Application to pharmacokinetic study in healthy and type 2 diabetic rats.

Trigonelline (TR), 4-hydroxyisoleucine (4-HI), and diosgenin (DG) are the main bioactives of the purified standardized extract of the popular plant Trigonella foenum-graecum L. (TFG), and it has been proven effective for the treatment of various diseases. However, to the best of our knowledge, no study has investigated the pharmacokinetic parameters of purified standardized T. foenum-graecum extract in normal and diabetic Wistar rats. The present study has developed and validated a rapid, reliable, and sensitive simultaneous ultra-performance liquid chromatography MS method to estimate these bioactives. The chromatographic separation was achieved using methanol, acetonitrile, and 0.1% formic acid with the ideal gradient flow system on a BEH Shield RP 18 column. A positive electrospray ionization mode was selected to estimate m/z values of TR (138.14 > 94.63), 4-HI (148.19 > 74.08), and DG (415.54 > 271.33). The method was robust and reproducible over the linearity range of 60-5000, 6-5000, and 15-5000 ng/mL for TR, 4-HI, and DG, respectively. Using this novel validated method, we investigated the pharmacokinetic parameters of bioactives using Phoenix WinNonlin version 8.0 (Certera) in normal and diabetic rats. The assay was successfully applied for the estimation of pharmacokinetic parameters using noncompartmental analysis. This investigation shows that the absorption rate increased, whereas distribution and elimination processes slowed down in diabetic rats compared with normal rats.

Plasma Heating Induced by Tadpole-like Downflows in the Flaring Solar Corona.

As one of the most spectacular energy release events in the solar system, solar flares are generally powered by magnetic reconnection in the solar corona. As a result of the re-arrangement of magnetic field topology after the reconnection process, a series of new loop-like magnetic structures are often formed and are known as flare loops. A hot diffuse region, consisting of around 5-10 MK plasma, is also observed above the loops and is called a supra-arcade fan. Often, dark, tadpole-like structures are seen to descend through the bright supra-arcade fans. It remains unclear what role these so-called supra-arcade downflows (SADs) play in heating the flaring coronal plasma. Here we show a unique flare observation, where many SADs collide with the flare loops and strongly heat the loops to a temperature of 10-20 MK. Several of these interactions generate clear signatures of quasi-periodic enhancement in the full-Sun-integrated soft X-ray emission, providing an alternative interpretation for quasi-periodic pulsations that are commonly observed during solar and stellar flares.

Generation of solar spicules and subsequent atmospheric heating.

Spicules are rapidly evolving fine-scale jets of magnetized plasma in the solar chromosphere. It remains unclear how these prevalent jets originate from the solar surface and what role they play in heating the solar atmosphere. Using the Goode Solar Telescope at the Big Bear Solar Observatory, we observed spicules emerging within minutes of the appearance of opposite-polarity magnetic flux around dominant-polarity magnetic field concentrations. Data from the Solar Dynamics Observatory showed subsequent heating of the adjacent corona. The dynamic interaction of magnetic fields (likely due to magnetic reconnection) in the partially ionized lower solar atmosphere appears to generate these spicules and heat the upper solar atmosphere.

Triggering The Birth of New Cycle's Sunspots by Solar Tsunami.

When will a new cycle's sunspots appear? We demonstrate a novel physical mechanism, namely, that a "solar tsunami" occurring in the Sun's interior shear-fluid layer can trigger new cycle's magnetic flux emergence at high latitudes, a few weeks after the cessation of old cycle's flux emergence near the equator. This tsunami is excited at the equator when magnetic dams, created by the oppositely-directed old cycle's toroidal field in North and South hemispheres, break due to mutual annihilation of toroidal flux there. The fluid supported by these dams rushes to the equator; the surplus of fluid cannot be contained there, so it reflects back towards high latitudes, causing a tsunami. This tsunami propagates poleward at a speed of ~300 m/s until it encounters the new cycle's spot-producing toroidal fields in mid-latitudes, where it perturbs the fields, triggering their surface-eruption in the form of new cycle spots. A new sunspot cycle is preceded for several years by other forms of high-latitude magnetic activity, such as coronal bright points and ephemeral regions, until the tsunami causes the birth of new cycle's spots. The next tsunami is due by 2020, portending the start of intense 'space weather' that can adversely impact the Earth.

Evaluation of herb-drug interaction of a polyherbal Ayurvedic formulation through high throughput cytochrome P450 enzyme inhibition assay.

ETHNOPHARMACOLOGICAL RELEVANCE: Arishtas are Ayurvedic formulation made with decoction of herbs. Arjunarishta formulation is being used in Ayurveda for cardio-protective activity. Ashwagandharishta formulation possesses antioxidant, anti-atherosclerotic and anti-stress properties. Ridayarishta, a novel empirical formulation was prepared using combination of selected ingredients from these two formulations to support healthy heart functions and to reduce stress. AIM OF THE STUDY: Aim of the Study was to investigate herb-drug interaction (HDI) of Ridayarishta formulation through human hepatic cytochrome P450 (CYP450) enzyme inhibition assay. MATERIALS AND METHODS: Ridayarishta formulation was phyto-chemically standardized against arjunolic acid, arjunetin, berberine, piperine, resveratrol and withaferin-A using high performance thin layer chromatography (HPTLC) analysis. The formulation was standardized with respect to ethanol by gas chromatographic (GC) analysis. HDI was evaluated with Ridayarishta formulation and amlodipine besilate, atenolol, atorvastatin, metformin, glipizide glimepiride cocktail using high throughput CYP450 enzyme inhibition assay; against CYP1A2, 2C19, 2D6 and 3A4 isozymes. RESULTS: Contents of arjunolic acid, arjunetin, berberine, piperine, resveratrol and withaferin-A in Ridayarishta formulation were found to be 1.76±0.12, 1.51±0.09, 1.85±0.05, 3.2±0.12, 1.21±0.08, and 2.16±0.09ppm, respectively. Quantity of ethanol in Ridayarishta was found to be 7.95±0.023% (V/V). Ridayarishta showed significantly higher (P<0.001) IC50 value against CYP1A2 (IC50-13.80±1.96µg/mL), 2C19 (IC50-14.343±2.28µg/mL), 2D6 (IC50-0.897±0.28µg/mL) and 3A4 (IC50-32.057±2.51µg/mL) compared to positive controls such as furafylline, tranylcypromine, quinidine and ketoconazole respectively. Cocktail of herbal formulation and cardio protective, antihypertensive, anti-diabetic drugs showed significantly (P<0.001and P<0.01) less or negligible HDI. CONCLUSION: Ridayarishta formulation alone and cocktail with amlodipine besilate, atenolol, atorvastatin, metformin, glipizide, glimepiride had negligible or insignificant effect on CYP450 inhibition. It may be concluded that consumption of Ridayarishta along with selective cardio protective, antihypertensive and anti-diabetic conventional medicine is safe with negligible or without any significant CYP450 (CYP1A2, 2C19, 2D6 and 3A4) inhibition mediated HDI.

Is surgical intervention for ectopic pregnancy in a low resource set-up avoidable?

BACKGROUND: Ectopic pregnancy is one of the most common life threatening complications in the first trimester of pregnancy having significant adverse effects on future pregnancy outcome, particularly if salpingectomy is used as the modality of treatment. So medical management is now advocated. For that, cases need to be diagnosed at an earlier stage. Keeping these backgrounds in mind we took up this study to look into the feasibility of conservative management- both medical and surgical - in a tertiary care centre. AIMS: To find out the demographic profile and risk factors of the ectopic pregnancy cases; the clinical presentation of the cases; the mode of treatment offered to the patients. MATERIALS AND METHODS: It was a record based retrospective study.All the patients diagnosed as ectopic pregnancy in a tertiary care hospital from January, 2011 to December, 2012, was included in the study. RESULTS: A total of 234 ectopic cases (1.5% of total deliveries) were recorded, constituting 5.4% of total gynaecological emergencies of this institute. Majority of patients were multigravida (74.4%) and of age group of 26-30years (35.9%). Fallopian tube was the most common site (99.1%) with only two cases in ovary. Ampulla (71.4%) was found to be most frequent site for implantation in fallopian tube. Pelvic inflammatory diseases (38.5%) and past history of induced abortion (35.9%) were major risk factors. Most patients (63.3%) did not use any contraceptives and 30.3% patients used OCP intermittently. No patient presented before 4weeks of gestation, while 69.2% presented between 4-7weeks and the rest beyond 7week. They presented with shock in 44.9% cases. Surgical treatment was offered in 98.3% cases, while medical treatment was offered to only four cases. CONCLUSION: There is a huge surgical burden due to ectopic pregnancy impinging on our hospital resources. Surgery is resorted to indiscriminately for even those cases that could have been medically treated otherwise. Hence, the need to change the mindset of the care-providers at all levels to opt for medical management of ectopic pregnancy wherever applicable.

Quantitative strain and compositional studies of InxGa1-xAs Epilayer in a GaAs-based pHEMT device structure by TEM techniques.

In GaAs-based pseudomorphic high-electron mobility transistor device structures, strain and composition of the In x Ga1-x As channel layer are very important as they influence the electronic properties of these devices. In this context, transmission electron microscopy techniques such as (002) dark-field imaging, high-resolution transmission electron microscopy (HRTEM) imaging, scanning transmission electron microscopy-high angle annular dark field (STEM-HAADF) imaging and selected area diffraction, are useful. A quantitative comparative study using these techniques is relevant for assessing the merits and limitations of the respective techniques. In this article, we have investigated strain and composition of the In x Ga1-x As layer with the mentioned techniques and compared the results. The HRTEM images were investigated with strain state analysis. The indium content in this layer was quantified by HAADF imaging and correlated with STEM simulations. The studies showed that the In x Ga1-x As channel layer was pseudomorphically grown leading to tetragonal strain along the [001] growth direction and that the average indium content (x) in the epilayer is ~0.12. We found consistency in the results obtained using various methods of analysis.

Hemophagocytic syndrome secondary to cytomegalovirus infection in an infant.

Virus associated hemophagocytic syndrome is a non-neoplastic, generalized histiocytic proliferation with prominent hemophagocytosis associated with a systemic viral infection. We report a case of cytomegalovirus (CMV) associated hemophagocytic syndrome in a 2 month old male child presenting with rashes, fever, hepatosplenomegaly, cervical lymphadenopathy and pancytopenia. Fine needle aspiration cytology and biopsy from cervical lymph nodes revealed prominent hemophagocytosis. Serology for CMV IgM was positive in both the mother and the child, suggesting recent infection. Possibly there was intrauterine transmission of the infection.

HRQoL in HIV-infected children using PedsQL 4.0 and comparison with uninfected children.

PURPOSE: To assess the reliability and validity of Pediatric Quality of Life Inventory 4.0 (PedsQL(TM) 4.0) in children living with HIV. Also to determine the association of HIV infection, treatment regimens, and type of care received on quality of life (QoL) in pediatric patients. METHODS: Study was conducted from January to December 2008 at Dr. Ram Manohar Lohia Hospital, New Delhi, India at the HIV pediatric outpatient department (OPD). PedsQL(TM) 4.0 was administered to 100 HIV-infected and 200 uninfected children aged 8-12 years and their primary caregivers. RESULTS: Internal consistency reliability exceeded 0.70 for both proxy-reported and self-reported scales. Intraclass correlation coefficient demonstrated mainly larger values for parent proxy-report (interval of 0.926-0.952 with 95% confidence) than for child self-report (interval of 0.891-0.928 with 95% confidence). Factor analysis was performed and it indicated that five factors were extracted from the PedsQL(TM) 4.0 and these five factors correspond mainly to the five scales. HIV infection was associated with a negative impact on QoL among children with lower scores for physical, school, and emotional functioning and health symptoms. In contrast, uninfected children had lower social functioning scores. Our results showed antiretroviral treatment to be associated with improved QoL among HIV-infected children. We even identified infected children living at home to be at a higher distress of psychosocial functioning and health symptoms when compared with children living in care homes. CONCLUSIONS: PedsQL(TM) is an acceptable and valid measure of health-related quality of life (HRQoL) for HIV-infected children and uninfected group. Application of this data will be helpful for program managers to devise care and support programme for both infected and uninfected children.

Sensitivity of paediatric AIDS score vs. WHO case classification in Indian children--a retrospective study.

This study was conducted at the Department of Paediatrics, Dr Ram Manohar Lohia Hospital, to test the statistical significance of existing World Health Organization (WHO) clinical case definition (CCD) for diagnosis of AIDS in areas where diagnostic resources are limited. A total of 360 cases between 18 months and 12 years of age satisfying WHO case definitions of AIDS were included in study group. Our study detected 16.66% (60) of HIV incidence in children visiting the paediatrics outpatient clinic. Twenty percent of cases manifested three major and two minor signs, which had sensitivity of 73.33%; specificity, 90.66% and positive predictive value (PPV), 61.11%. Stepwise logistic analysis identified weight loss, chronic fever >1 month and total lymphocyte count <1500 cells mm(-3) as important predictors. Eighty-six cases (23.89%) showed two major and two minor signs with sensitivity and specificity of 86.66 and 88.66%, respectively. Thus a CCD based on 13 clinical signs/symptoms was proposed for paediatric AIDS with better sensitivity and PPV than the WHO case definition but with almost similar specificity.

Biotransformation of 3-hydroxydibenzo-alpha-pyrone into 3, 8 dihydroxydibenzo-alpha-pyrone and aminoacyl conjugates by Aspergillus niger isolated from native shilajit

Shilajit is a panacea in Ayurveda, the Indian traditional system of medicine. The major bioactives of shilajit have been identified as dibenzo-alpha-pyrones (DBPs), its oligomers and aminoacyl conjugated derivatives. These bioactive compounds play a crucial role in energy metabolism in all animal cells including those of man. 3-hydroxydibenzo-alpha-pyrone (3-OH-DBP), a key DBP component of shilajit is converted, among other products, to another active DBP derivative, viz. 3,8-hydroxydibenzo-alpha-pyrone, 3,8(OH)2-DBP, in vivo, when its precursor is ingested. 3,8(OH)2-DBP is then involved in energy synthesis in the mitochondria in the reduction and stabilization of coenzyme Q10 in the electron transport chain. As the chemical synthesis of 3,8(OH)2-DBP is a complex, multi-step process and economically not readily viable, we envisioned the development of a process using microorganisms for bioconversion of 3-OH-DBP to 3,8(OH)2-DBP. In this study, the biotransformation of 3-OH-DBP is achieved using Aspergillus niger, which was involved in the humification process on sedimentary rocks leading to shilajit formation. A 60 percent bioconversion of 3-OH-DBP to 3,8(OH)2-DBP and to its aminoacyl derivatives was achieved. The products were characterized and estimated by high performance liquid chromatography (HPLC), high performance flash chromatography (HPFC) and gas chromatography-mass spectrometry (GC-MS) analyses. Among the Aspergillus species isolated and identified from native shilajit, A. niger was found to be the most efficient for this bioconversion.

Shedding off specific lipid constituents from sperm cell membrane during cryopreservation.

Membrane damage is one of the main reasons for reduced motility and fertility of sperm cells during cryopreservation. Using a model system of sperm cryopreservation developed in our laboratory, we have investigated the detailed changes due to cryopreservation in the plasma membrane lipid composition of the goat epididymal sperm cells. Total lipid and its components, i.e., neutral lipids, glycolipids and phospholipids decreased significantly after cryopreservation. Among neutral lipids sterols, steryl esters and 1-O-alkyl-2,3-diacyl glycerols decreased appreciably, while among phospholipids, major loss was observed for phosphatidyl choline and phosphatidyl ethanolamine. Unsaturated fatty acids bound to the phospholipids diminished while the percentage of saturated acids increased. The cholesterol:phospholipid ratio enhanced and the amount of hydrocarbon, which was unusually high, increased further on cryopreservation. The data indicates that profound increase of the hydrophobicity of the cell membrane is one of the major mechanisms by which spermatozoa acquire potential to resist or combat stress factors like cryodamage. The results are compatible with the view that for survival against cryodamage, sperm cells modulate the structure of their outer membrane by shedding off preferentially some hydrophilic lipid constituents of the cell membrane.