Immunomodulatory Effects of a Herbo-Mineral Ayurvedic Formulation in Experimental Models.

BACKGROUND: Ayurveda, an ancient Indian system of medicine, encapsulates comprehensive principles and formulations for disease prevention and treatment. A herbo-mineral Ayurvedic formulation, IMMBO, comprising Mandoor Bhasma and 18 herbs has shown promising results in treating allergic rhinitis in clinical studies. OBJECTIVE: This discussed series of experimental studies were conducted to explore the immuno-modulatory potential of IMMBO. METHODOLOGY: A series of experimental studies were carried out in immunosuppressed rats to explore the immune-modulatory effects of IMMBO. RESULTS: IMMBO was effective in reinstating neutrophil activation, stimulating cellular and humoral immunity, and counteracting immunosuppression at the molecular level. The modulation of key signalling molecules, including tumour necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), interleukin-1 beta (IL-1ß), extracellular signal-regulated kinase (ERK), phosphoinositide 3-kinase (PI3K), and nuclear factor-kappa B (NF-κb), showcased the formulation's multifaceted impact. Additionally, its ability to block histamine release suggests potential in controlling allergic states, positioning it as a promising therapeutic candidate for immune-related disorders. However, the precise mode of action remains elusive, warranting further in-depth pharmacological studies. CONCLUSION: This research substantiates the ancient Ayurvedic wisdom using modern scientific parameters, endorsing IMMBO's potential as an immune-modulatory agent.

Proof of Efficacy Study to Evaluate an Ayurvedic Formulation in the Treatment of Allergic Rhinitis: An Open Label Randomized Controlled Clinical Trial.

BACKGROUND: Allergic rhinitis is largely treated by using antihistamines and nasal sprays, either alone or in combination. However, these measures ease out the symptoms but do not address causative factors, and have their share of side effects and limitations. An Ayurvedic herbo-mineral formulation, IMMBO, has been reported to be effective in treating allergic rhinitis. OBJECTIVE: The present study was carried out to evaluate the efficacy, safety, and tolerability of the Ayurvedic herbo-mineral formulation in comparison with a fixed-dose combination of levocetirizine and montelukast. METHOD: This was a randomized, comparative, clinical study carried out on 250 patients at a medical college in India. The patients were enrolled according to the eligibility criteria of the study and randomized into two groups, to receive either Ayurvedic herbo-mineral formulation, IMMBO, or a combination of levocetirizine and montelukast for 28 days. Total nasal symptom score (TNSS) and Immunoglobulin E (IgE) were calculated for evaluation of efficacy parameters.  Result: At the end of therapy both IMMBO and levocetirizine and montelukast combination showed significant improvement in TNSS in both treated population and per protocol population. The IMMBO group had a statistically higher reduction in TNSSs compared to the levocetirizine + montelukast group (-5.70 vs. -3.31; p<0.01). There was a statistically significant difference in the reduction of IgE levels between the groups (-351.54 vs. -208.79; p<0.05).  Conclusion: The findings of this study establish prima facie evidence about the efficacy and safety of Ayurvedic formulation. However, the said Ayurvedic formulation needs to be further developed scientifically.

Ayurvedic Treatment Protocol for Hereditary Pancreatitis: A Case Report Demonstrating Disease Arrestation.

The case report presented here highlights the use of an Ayurvedic treatment protocol (ATP) in managing hereditary pancreatitis (HP) in a 14-year-old boy. HP is a rare form of pancreatitis caused by specific gene mutations that are inherited within families. It is known to be aggressive and can lead to pancreatic cancer in later stages. The boy, in this case, experienced multiple episodes of pancreatitis and required several hospitalizations despite following a conventional treatment approach, which included a dairy-free, protein and fat-restricted diet, and pancreatic enzyme supplementation. However, after starting the ATP in February 2022, which involved a modified diet and the use of herbo-mineral Ayurvedic formulations, the boy reported significant improvement in his general well-being and was able to lead a normal life without experiencing any discomfort. The ATP included a customized diet comprising dairy products with moderate amounts of fat and protein, along with specific herbo-mineral formulations and the withdrawal of pancreatic enzymes. The boy also received vitamin D3 supplementation. After approximately one year of following the ATP, the disease progression was arrested, as indicated by follow-up images and investigations. The size of the pancreatic duct decreased from 8 mm to 2.8 mm. This case report suggests that the ATP may have potential efficacy in managing hereditary pancreatitis and halting disease progression. However, it is important to note that this is a single case report, and further research and clinical studies are needed to validate the long-term benefits and understand the underlying mechanisms of Ayurvedic interventions in hereditary pancreatitis.

The 2021 European Group on Graves' orbitopathy (EUGOGO) clinical practice guidelines for the medical management of Graves' orbitopathy.

Graves' orbitopathy (GO) is the main extrathyroidal manifestation of Graves' disease (GD). Choice of treatment should be based on the assessment of clinical activity and severity of GO. Early referral to specialized centers is fundamental for most patients with GO. Risk factors include smoking, thyroid dysfunction, high serum level of thyrotropin receptor antibodies, radioactive iodine (RAI) treatment, and hypercholesterolemia. In mild and active GO, control of risk factors, local treatments, and selenium (selenium-deficient areas) are usually sufficient; if RAI treatment is selected to manage GD, low-dose oral prednisone prophylaxis is needed, especially if risk factors coexist. For both active moderate-to-severe and sight-threatening GO, antithyroid drugs are preferred when managing Graves' hyperthyroidism. In moderate-to-severe and active GO i.v. glucocorticoids are more effective and better tolerated than oral glucocorticoids. Based on current evidence and efficacy/safety profile, costs and reimbursement, drug availability, long-term effectiveness, and patient choice after extensive counseling, a combination of i.v. methylprednisolone and mycophenolate sodium is recommended as first-line treatment. A cumulative dose of 4.5 g of i.v. methylprednisolone in 12 weekly infusions is the optimal regimen. Alternatively, higher cumulative doses not exceeding 8 g can be used as monotherapy in most severe cases and constant/inconstant diplopia. Second-line treatments for moderate-to-severe and active GO include (a) the second course of i.v. methylprednisolone (7.5 g) subsequent to careful ophthalmic and biochemical evaluation, (b) oral prednisone/prednisolone combined with either cyclosporine or azathioprine; (c) orbital radiotherapy combined with oral or i.v. glucocorticoids, (d) teprotumumab; (e) rituximab and (f) tocilizumab. Sight-threatening GO is treated with several high single doses of i.v. methylprednisolone per week and, if unresponsive, with urgent orbital decompression. Rehabilitative surgery (orbital decompression, squint, and eyelid surgery) is indicated for inactive residual GO manifestations.

Management of thyroid eye disease in the United Kingdom: A multi-centre thyroid eye disease audit.

This article aims to provide baseline data and highlight any major deficiencies in the current level of care provided for adult patients with thyroid eye disease (TED). We undertook a prospective, nonrandomized cross-sectional multicenter observational study. During a 3-month period June-August 2014, consecutive adult patients with TED who presented to nominated specialist eye clinics in the United Kingdom, completed a standardized questionnaire. Main outcome measures were: demographics, time from diagnosis to referral to tertiary centre, time from referral to review in specialist eye clinic, management of thyroid dysfunction, radioiodine and provision of steroid prophylaxis, smoking, and TED classification. 91 patients (mean age 47.88 years) were included. Female-to-male ratio was 6:1. Mean time since first symptoms of TED = 27.92 (73.71) months; from first visit to any doctor with symptoms to diagnosis = 9.37 (26.03) months; from hyperthyroidism diagnosis to euthyroidism 12.45 (16.81) months. First, 13% had received radioiodine. All those with active TED received prophylactic steroids. Seven patients who received radioiodine and did not have TED at the time went on to develop it. Then, 60% patients were current or ex-smokers. 63% current smokers had been offered smoking cessation advice. 65% patients had active TED; 4% had sight-threatening TED. A large proportion of patients (54%) were unaware of their thyroid status. Not enough patients are being provided with smoking cessation advice and information on the impact of smoking on TED and control of thyroid function.

Iodine supplementation in pregnancy - is it time?

Iodine is essential for the synthesis of thyroid hormone and optimal foetal neurological development. Pregnant women living in borderline or moderate-severe iodine deficient areas are at particularly high risk of being iodine deficient, and this may have important clinical consequences, particularly for the neurocognitive development of the offspring. It is a substantial problem and many countries including the United Kingdom are mild-moderately iodine deficient. Although the detrimental effects of severe iodine deficiency are well recognized, the benefits of correcting mild-to-moderate iodine deficiency are unclear due to a lack of randomized controlled trials in this area. However, observational data increasingly indicate that there may be substantial health and economic benefits from correcting iodine deficiency in pregnancy. There is now a growing trend from learned societies that iodine supplementation should be utilized in pregnancy in countries with mild-to-moderate iodine deficiency. The dose of iodine supplement needs to reflect local iodine status and iodization policies and will need careful monitoring at the population level to ensure doses to prevent under/excess dosing which would undermine the potential benefits. National tailored guidance is therefore essential.

Management of patients in a combined thyroid eye clinic in secondary care.

The European Group on Graves' Orbitopathy (EUGOGO) recommends the use of specialised multidisciplinary clinics for the management of thyroid eye disease (TED). In the UK, many patients with TED are managed outside of specialised clinics. We describe the organisation of a combined TED clinic in a secondary care setting and present the result of a prospective audit of the patient characteristics and outcomes during the first four years of a combined TED clinic. Of a total of 132 patients referred to the TED clinic, 114 (86 %) had TED (90 females, median age 56 years; range 17-90 years). At presentation, 77 (67 %) were current or ex-smokers and 99 (87 %) were biochemically euthyroid. Median duration of eye symptoms was 12 months. Fifty-two percent, 45 and 3 had mild, moderate-to-severe and sight-threatening TED, respectively. Only 18 % of patients had a clinical activity score (CAS) of ≥3. Sixty-nine patients (61 %) required follow-up appointments in the TED clinic. In those who required follow-up, 43 % (n = 30) received either immunosuppressive or surgical treatment. CAS improved from first to final visit, with 29 % (n = 20) having a CAS of ≥3 at the first visit and 1 % (n = 1) at the final visit (p = 0.0001). There was also a decrease in prevalence of smoking and thyroid dysfunction at the final visit. A multidisciplinary specialised TED clinic offers an optimal setting for managing patients with TED; however, patients are often referred late to a specialist TED clinic.

2012 European thyroid association guidelines for the management of familial and persistent sporadic non-autoimmune hyperthyroidism caused by thyroid-stimulating hormone receptor germline mutations.

All cases of familial thyrotoxicosis with absence of evidence of autoimmunity and all children with persistent isolated neonatal hyperthyroidism should be evaluated for familial non-autoimmune autosomal dominant hyperthyroidism (FNAH) or persistent sporadic non-autoimmune hyperthyroidism (PSNAH). First, all index patients should be analysed for the presence/absence of a thyroid-stimulating hormone (TSH) receptor (TSHR) germline mutation, and if they display a TSHR germline mutation, all other family members including asymptomatic and euthyroid family members should also be analysed. A functional characterization of all new TSHR mutations is necessary. Appropriate ablative therapy is recommended to avoid relapses of hyperthyroidism and its consequences, especially in children. Therefore, in children the diagnosis of FNAH or PSNAH needs to be established as early as possible in the presence of the clinical hallmarks of the disease.

Carbimazole embryopathy: implications for the choice of antithyroid drugs in pregnancy.

Maternal thyrotoxicosis, predominantly secondary to Graves' disease, affects 0.2% of all pregnancies. The Endocrine Society guidelines recommend the use of propylthiouracil as a first-line drug for thyrotoxicosis in pregnancy because of associations between carbimazole or methimazole and congenital anomalies. However, recent studies have highlighted the risk of severe liver injury with propylthiouracil. Here, we report another case with multiple congenital anomalies following in utero exposure to carbimazole and review the literature to consider the risks and benefits of available pharmacological treatments for thyrotoxicosis in pregnancy.

Orbital decompression for Graves' orbitopathy in England.

AIMS: The purpose of this study was to obtain data on orbital decompression procedures performed in England, classed by hospital and locality, to evaluate regional variation in care. METHODS: Data on orbital decompression taking place in England over a 2-year period between 2007 and 2009 were derived from CHKS Ltd and analysed by the hospital and primary care trust. RESULTS AND CONCLUSIONS: In all, 44% of these operations took place in hospitals with an annual workload of 10 or fewer procedures. Analysis of the same data by primary care trust suggests an almost 30-fold variance in the rates of decompression performed per unit population. Expertise available to patients with Graves' orbitopathy and rates of referral for specialist care in England appears to vary significantly by geographic location. These data, along with other outcome measures, will provide a baseline by which progress can be judged.

Unusual cause of severe knee pain.

MRI is the preferred modality to investigate seizure as diagnostic yield is higher and more specific due to its varied applications. Total of 160 brain MR images of patients suffering from seizure during one year period was evaluated. All seizure cases underwent specific protocol for imaging that targeted hippocampal/mesial temporal lobe imaging.

Anti-cyclic citrullinated peptide antibodies in juvenile idiopathic arthritis.

OBJECTIVE: Prevalence and clinical significance of anti-cyclic citrullinated peptide (CCP) antibodies in Indian patients with juvenile idiopathic arthritis (JIA). METHODS: Anti-CCP antibodies were determined by enzyme-linked immunosorbent assay (ELISA) in 78 patients with JIA which included all 3 major subtypes of the disease: pauciarticular, polyarticular afld systemic onset. Values above 5 relative units were taken as positive. Associations between anti-CCP antibodies and clinical and laboratory and radiological parameters were determined. RESULTS: Anti-CCP antibodies were positive in only 2 of 34 (5.9%) patients with pauciarticular JIA and 3 of 17 (17.6%) of systemic,.pnset JIA, whereas it was positive in 13 of 27 (48.1%) of polyarticular JIA patients (p < 0.001). Furthermore, it was seen that among patients with polyarticular JIA, RF-lgM positive patients had higher rate of anti-CCP antibody positivity with 7 of 8 (87.5%) patients having positive anti-CCP antibody (p<0.001). Similarly, patients with erosions (11/19; p<0.001) and deformities (5/-10; p<0.001) were found to have significant association with anti-CCP antibody positivity. CONCLUSION: Anti-CCP antibodies could be detected more frequently in the sera of JIA patients with severe manifestations like-erosions and deformity. It was also more significantly associated with seropositive polyarticular JIA than other types. It can be presumed from these results that anti-CCP antibodies can be used as a marker to predict severe course of JIA at the onset to guide optimal aggressive therapy.

Targeted intracellular delivery of therapeutics: an overview.

During the last decade, intracellular drug delivery has become an emerging area of research in the medical and pharmaceutical field. Many therapeutic agents such as drugs and DNA/oligonucleotides can be delivered not just to the cell but also to a particular compartment of that cell to achieve better activity e.g. proapoptotic drugs to the mitochondria, antibiotics and enzymes to the lysosomes and various anticancer drugs and gene to the nucleus. The lipidic nature of biological membrans is the major obstacle to the intracellular delivery of macromolecular and ionic drugs. Additionally, after endocytosis, the lysosome, the major degradation compartment, needs to be avoided for better activity. To avoid these problems, various carriers have been investigated for efficient intracellular delivery, either by direct entry to cytoplasm or by escaping the endosomal compartment. These include cell penetrating peptides, and carrier systems such as liposomes, cationic lipids and polymers, polymeric nanoparticles, etc. Various properties of these carriers, including size, surface charge, composition and the presence of cell specific ligands, alter their efficacy and specificity towards particular cells. This review summarizes various aspects of targeted intracellular delivery of therapeutics including pathways, mechanisms and approaches. Various carrier constructs having potential for targeted intracellular delivery are also been discussed.