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1.
J Family Med Prim Care ; 12(10): 2516-2519, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38074274

RESUMO

Herpes zoster (HZ) is a manifestation of the reactivation of latent varicella zoster virus (VZV) infection in the dorsal root ganglion. The occurrence of HZ has been reported in association with COVID-19. Herein, we describe 10 cases who developed classic HZ within 2-3 weeks of acquiring COVID-19 infection. The triggers in these patients could be severe stress (related to quarantine issues, fear of hospitalisation and death) immune dysregulation and systemic steroid therapy in treating COVID-19. The clinical patterns and therapeutic responses observed were similar to HZ in immunocompetent persons. Increased expression of NKG2A on NK and CD8+ T cells has been proposed as a pathophysiologic mechanism in triggering HZ at the molecular level in COVID-19 patients. Primary physicians should be aware of this association to counsel and treat such patients appropriately, as initiating early treatment could minimise the risk of complications like postherpetic neuralgia.

2.
Molecules ; 28(9)2023 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-37175309

RESUMO

The main objective of this research was to develop novel compounds from readily accessed natural products especially eugenol with potential biological activity. Eugenol, the principal chemical constituent of clove (Eugenia caryophyllata) from the family Myrtaceae is renowned for its pharmacological properties, which include analgesic, antidiabetic, antioxidant, anticancer, and anti-inflammatory effects. According to reports, PPARγ regulates inflammatory reactions. The synthesized compounds were structurally analyzed using FT-IR, 1HNMR, 13CNMR, and mass spectroscopy techniques. Molecular docking was performed to analyze binding free energy and important amino acids involved in the interaction between synthesized derivatives and the target protein. The development of the structure-activity relationship is based on computational studies. Additionally, the stability of the best-docked protein-ligand complexes was assessed using molecular dynamic modeling. The in-vitro PPARγ competitive binding Lanthascreen TR-FRET assay was used to confirm the affinity of compounds to the target protein. All the synthesized derivatives were evaluated for an in vitro anti-inflammatory activity using an albumin denaturation assay and HRBC membrane stabilization at varying concentrations from 6.25 to 400 µM. In this background, with the aid of computational research, we were able to design six novel derivatives of eugenol synthesized, analyzed, and utilized TR-FRET competitive binding assay to screen them for their ability to bind PPARγ. Anti-inflammatory activity evaluation through in vitro albumin denaturation and HRBC method revealed that 1f exhibits maximum inhibition of heat-induced albumin denaturation at 50% and 85% protection against HRBC lysis at 200 and 400 µM, respectively. Overall, we found novel derivatives of eugenol that could potentially reduce inflammation by PPARγ agonism.


Assuntos
Eugenol , PPAR gama , Humanos , Eugenol/farmacologia , PPAR gama/metabolismo , Simulação de Acoplamento Molecular , Agonistas PPAR-gama , Espectroscopia de Infravermelho com Transformada de Fourier , Anti-Inflamatórios/farmacologia , Inflamação , Relação Estrutura-Atividade , Simulação de Dinâmica Molecular , Albuminas
3.
J Family Med Prim Care ; 11(5): 2214-2216, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35800561

RESUMO

Nevus flammeus is the most common benign congenital capillary malformation, often known as a port-wine stain. Sturge-Weber syndrome (SWS) is a congenital, sporadic, nonfamilial disease characterized by intracranial and ophthalmic vascular anomalies and nevus flammeus. It usually manifests as developmental delay, learning problems, paralysis, seizures, glaucoma and attention deficit, and hyperactivity disorder. A 29-year-old male patient presented with a reddish patch over the face since birth. He was found to have hemihypertrophy of face, hemiparesis of right limbs, and low intelligence quotient. On ophthalmic examination, the patient was found to have glaucoma and only perception of light in the left eye. Computed tomography brain showed atrophy of the left cerebral hemisphere and calcifications in the left frontal, parietal and occipital regions. With these findings, he was diagnosed as SWS type I. A multidisciplinary approach was followed for patient evaluation and management. This case also highlights the irreversible sequelae of this rare phacomatosis.

4.
J Family Med Prim Care ; 11(3): 1195-1197, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35495808

RESUMO

Porokeratosis is a keratinization disorder characterized by hyperkeratotic sharply demarcated plaques with central atrophy and histopathologically, by cornoid lamella. A 30-year-old male presented with multiple pruritic dark raised skin lesions over the trunk, face, and upper limbs for past 3 years. Cutaneous examination revealed hyperkeratotic annular plaques with raised margins over face, trunk, and arms. Histopathology revealed marked hyperkeratosis with irregular acanthosis and papillomatosis. Vertical parakeratotic foci and focal hypergranulosis were seen. Hence, a diagnosis of disseminated superficial porokeratosis was made. We present this rare case which may have association with systemic disease, immunosuppression, and malignant transformation.

5.
J Family Med Prim Care ; 11(12): 7972-7974, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36994043

RESUMO

Increased laxity of the skin can be caused by aging, significant weight loss, or defects in the elastic tissue. A 38-year-old female presented with increased laxity of the skin over the neck, thighs, and abdomen for 6 years, associated with headache and blurring of vision for a week. On cutaneous examination, prominent skin folds, laxity, and wrinkles were noted over the neck, abdomen, thighs, and groin, with yellowish papules along the neck creases. Ocular examination revealed features suggestive of angioid streaks. Skin biopsy showed fragmented elastic fibers and intervening calcium deposits on Verhoeff Van Gieson and Von Kossa stains. Based on these findings, a diagnosis of pseudoxanthoma elasticum (PXE) was made. The patient was started on oral and topical sunscreens and eye protection and advised regular follow-up. Diagnosing the condition early based on skin findings can help prevent further multi-system manifestations by taking appropriate preventive measures as this condition is progressive and has no cure.

6.
Curr Neuropharmacol ; 20(5): 893-915, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34751120

RESUMO

Peroxisome proliferator-activated receptors (PPARs) activity has significant implications for the development of novel therapeutic modalities against neurodegenerative diseases. Although PPAR-α, PPAR-ß/δ, and PPAR-γ nuclear receptor expressions are significantly reported in the brain, their implications in brain physiology and other neurodegenerative diseases still require extensive studies. PPAR signaling can modulate various cell signaling mechanisms involved in the cells contributing to on- and off-target actions selectively to promote therapeutic effects as well as the adverse effects of PPAR ligands. Both natural and synthetic ligands for the PPARα, PPARγ, and PPARß/δ have been reported. PPARα (WY 14.643) and PPARγ agonists can confer neuroprotection by modulating mitochondrial dynamics through the redox system. The pharmacological effect of these agonists may deliver effective clinical responses by protecting vulnerable neurons from Aß toxicity in Alzheimer's disease (AD) patients. Therefore, the current review delineated the ligands' interaction with 3D-PPARs to modulate neuroprotection, and also deciphered the efficacy of numerous drugs, viz. Aß aggregation inhibitors, vaccines, and γ-secretase inhibitors against AD; this review elucidated the role of PPAR and their receptor isoforms in neural systems, and neurodegeneration in human beings. Further, we have substantially discussed the efficacy of PPREs as potent transcription factors in the brain, and the role of PPAR agonists in neurotransmission, PPAR gamma coactivator-1α (PGC-1α) and mitochondrial dynamics in neuroprotection during AD conditions. This review concludes with the statement that the development of novel PPARs agonists may benefit patients with neurodegeneration, mainly AD patients, which may help mitigate the pathophysiology of dementia, subsequently improving overall the patient's quality of life.


Assuntos
Doença de Alzheimer , Doenças Neurodegenerativas , Tiazolidinedionas , Reposicionamento de Medicamentos , Humanos , Ligantes , Dinâmica Mitocondrial , Simulação de Dinâmica Molecular , Doenças Neurodegenerativas/tratamento farmacológico , Doenças Neurodegenerativas/metabolismo , Oxirredução , PPAR alfa/agonistas , PPAR alfa/metabolismo , PPAR alfa/uso terapêutico , PPAR gama/agonistas , Qualidade de Vida , Tiazolidinedionas/uso terapêutico
7.
Neurotox Res ; 37(3): 508-524, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31782098

RESUMO

In the present study, two structurally diverse novel glitazones were designed and synthesized for activation of central PGC-1α signaling through stimulation of PPAR-γ receptor. The functional interaction between PGC-1α and PPAR-γ is a key interaction in the normal physiology of neuroprotective mechanism. Therefore, activation of PPAR-γ-dependent PGC-1α co-activator signaling could be an effective strategy to exhibit neuroprotection in several neurodegenerative disorders like Alzheimer's disease, Parkinson's disease, and cerebral ischemia. As part of rational design, analogs were designed manually based on principles of bioisosterism, followed by virtually screened using docking to predict the mode of interaction of compound towards the binding site and molecular dynamic simulation to observe the structural changes that occur during compound interaction with active site. The designed two glitazones (G1, G2) were synthesized and structurally analyzed. As part of evaluation, synthesized glitazones were subjected for preliminary neuroprotective evaluation in Lipopolysaccharide (LPS) intoxicated SH-SY5Y neuroblastoma cells. The results indicate that pre-treatment with synthesized glitazones have increased the percentage cell viability, protected the cell morphology, and decreased the release of pro-inflammatory cytokines (IL-1ß, TNF-α), lipid peroxide (LPO), and nitric oxide (NO) level in LPS intoxicated SH-SY5Y cells. Interestingly, among the two glitazones, G2 has shown significant neuroprotection in comparison to G1 and neuroprotective effect exerted by G2 was similar and comparable with the standard pioglitazone. Altogether, neuroprotection exhibited by this non-thiazolidione-based glitazones during neuroinflammatory conditions may be attributed to the activation of central PGC-1α signaling via PPAR-γ receptor.


Assuntos
Desenho de Fármacos , Doenças Neurodegenerativas/tratamento farmacológico , Fármacos Neuroprotetores/administração & dosagem , Fármacos Neuroprotetores/síntese química , PPAR gama/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Tiazolidinedionas/administração & dosagem , Tiazolidinedionas/síntese química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Encefalite/complicações , Encefalite/metabolismo , Humanos , Interleucina-1beta/metabolismo , Lipopolissacarídeos/administração & dosagem , Simulação de Dinâmica Molecular , Doenças Neurodegenerativas/complicações , Doenças Neurodegenerativas/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
8.
Indian J Dermatol ; 60(1): 33-40, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25657394

RESUMO

UNLABELLED: Acne vulgaris is a chronic condition affecting more than 85% of adolescents and young adults. It is one of the most common diseases affecting humanity and its impact on quality of life (QoL) is important. The impact of acne on QoL in Indian patients remains undocumented. The study was undertaken to detect the impact of acne vulgaris and related factors that may influence the QoL. MATERIALS AND METHODS: This was a hospital-based, prospective, cross-sectional, prestructured, questionnaire-based study done on 140 consenting individuals, who attended the Dermatology outpatient department. Acne vulgaris was graded using simple grading system. QoL was measured using a combination of skin disease-specific (Dermatological Life Quality Index (DLQI)) and acne-specific (Cardiff Acne Disability Index (CADI)) questionnaires. RESULTS: Majority of our study population were students (103, 73.6%). Face (139, 99.3%) was the commonest site of acne and comedones 133, 95% were the commonest type of lesion. Most of the individuals 66, 47.1% were observed to have grade 1 acne. The mean DLQI score was 6.91 and the mean CADI score was 5.2. Association between the scores was statistically significant. Age, occupation, marital status, family, and treatment history played a role in affecting the QoL. Diet, smoking, and alcohol did not influence the QoL. CONCLUSION: Though acne had impact on patient's QoL, it was less severe in our study. It is important for health professionals to incorporate QoL measurements when managing acne patients to provide better and appropriate care.

9.
Indian J Dermatol ; 57(5): 343-52, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23112352

RESUMO

BACKGROUND: Skin is a window to aging changes, a biological reality. There is a dearth of studies regarding the various chronological (intrinsic) aging and photoaging (extrinsic) changes seen in Asians. This study was undertaken to detect the clinical pattern of aging skin changes and dermatoses seen in the elderly. MATERIALS AND METHODS: This was a descriptive study conducted on 500 consecutive elderly individuals attending the Dermatology out-patient department. The severity of photoaging was graded using Glogau scale. RESULTS: Most of the population had skin type IV and V. Majority (415, 83%) of our cases had chronological aging without photoaging and the remaining 85 (17%) individuals had photoaging along with chronological aging. The common skin changes due to chronological aging were thin skin, fine wrinkles, xerosis, and loss of elasticity. Photoaging changes such as dyspigmentation, freckles, thick skin, deep wrinkles, melasma, citrine skin, senile purpura, pseudostellate scar, acrokeratoelastoidosis marginalis, and lentigines were less frequent in our study. Smoking and prolonged sun exposure was the risk factors aggravating photoaging. The most common dermatosis was pruritus in 248 (49.6%) individuals, of which 149 (29.8%) had pruritus associated with xerosis. Contact dermatitis was more common in males. Fungal infections were frequently seen in females. Seborrhoeic keratosis (253, 50.6%) was the most common benign neoplasm more commonly seen in males. Cutaneous malignancies were less common in our study population. CONCLUSION: Photoaging changes were less common than chronological aging changes in skin type IV. Chronological changes were more frequent in females than males, while photoaging was more frequent in males.

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