Mohammad Akram

Protein Misfolding and Aggregation in Alzheimer's Disease and Type 2 Diabetes Mellitus

In general, proteins can only execute their various biological functions when they are appropriately folded. Their amino acid sequence encodes the relevant information required for correct three-dimensional folding, with or without the assistance of chaperones. The challenge associated with understanding protein folding is currently one of the most important aspects of the biological sciences. Misfolded protein intermediates form large polymers of unwanted aggregates and are involved in the pathogenesis of many human diseases, including Alzheimers disease (AD) and Type 2 diabetes mellitus (T2DM). AD is one of the most prevalent neurological disorders and has worldwide impact; whereas T2DM is considered a metabolic disease that detrementally influences numerous organs, afflicts some 8% of the adult population, and shares many risk factors with AD. Research data indicates that there is a widespread conformational change in the proteins involved in AD and T2DM that form β-sheet like motifs. Although conformation of these β-sheets is common to many functional proteins, the transition from α-helix to β-sheet is a typical characteristic of amyloid deposits. Any abnormality in this transition results in protein aggregation and generation of insoluble fibrils. The abnormal and toxic proteins can interact with other native proteins and consequently catalyze their transition into the toxic state. Both AD and T2DM are prevalent in the aged population. AD is characterized by the accumulation of amyloid-β (Aβ) in brain, while T2DM is characterized by the deposition of islet amyloid polypeptide (IAPP, also known as amylin) within beta-cells of the pancreas. T2DM increases pathological angiogenesis and immature vascularisation. This also leads to chronic cerebral hypoperfusion, which results in dysfunction and degeneration of neuroglial cells. With an abundance of common mechanisms underpinning both disorders, a significant question that can be posed is whether T2DM leads to AD in aged individuals and the associations between other protein misfolding diseases.

A proteomic approach for exploring biofilm in Streptococcus mutans.

Biofilm formation by Streptococcus mutans is considered as its principal virulence factor, causing dental caries. Mutants of S. mutans defective in biofilm formation were generated and analyzed to study the collective role of proteins in its formation. Mutants were characterized on the basis of adherence to saliva-coated surface, and biofilm formation. The confocal laser microscopy and scanning electron microscopy images showed that the control biofilms had cluster of cells covered by layer of exo-polysaccharide while the biofilms of mutants were thin and spaced. Two-dimensional protein electrophoresis data analysis identified 57 proteins that are either up (44 proteins) or down (13 proteins) regulated. These data points to the importance of up and down regulated proteins in the formation of biofilm in Streptococcus mutans.

Kinetics and Mechanism of the Reaction of Ninhydrin with Chromium(III)-tryptophan Complex in Absence and Presence of Surfactants

Abstract The kinetics of the title reaction have been investigated in both aqueous and micellar cetyltrimethylammonium bromide(CTAB) solutions. Rate data indicate that the reaction follows the template mechanism in both the media. The observed rate constant is affected by [CTAB] changes and the maximum rate enhancement is ca. 4 -fold. The following parameters have been calculated at pH 5.0: for aqueous, kobs = 5.6 χ 10-5 s-1, ΔH* = 61 k J mol-1, ΔS* = -122 J K-1mol-1 ; for CTAB , kΨ = 24.7 χ 10-5 s-1 , ΔH* = 35 k J mol-1, ΔS* = -200 J K-1 mol-1, which reveal CTAB behaving as a catalyst. To explain the dependence of the reaction rate on [CTAB], pseudo-phase model proposed by Menger and Portnoy and modified by Bunton and Rodenas was used. The catalytic role of CTAB can be related to the extent of incorporation or association of the chromium(III)-tryptophan and ninhydrin into the micelles. Various factors which affect km, Ks KN and are discussed taking into account the micellar surface solvent properties.

Kinetics and Mechanism of the Reaction of Copper(II)-tryptophan Complex with Ninhydrin in Aqueous and Micellar Media

Kinetics of the title reaction has been investigated spectrophotometrically in aqueous solution as well as in the presence of cetyltrimethylammonium bromide (CTAB) cationic micelles. The reaction rate is first- and fractional-order with respect to [substrate] and [ninhydrin], respectively, both in the absence and presence of cationic micelles. Whereas SDS addition shows formation of a different product, the reaction of copper(II)-tryptophan complex with ninhydrin is catalyzed by CTAB: the maximum rate enhancement being ca . 5-fold. The data are interpreted in terms of the pseudo-phase model (assuming the association/incorporation of both the reactants at the micellar surface). The binding constants of copper(II)-tryptophan ( K S ) and ninhydrin ( K N ) with CTAB micelles have been calculated. The presence of inorganic salts (NaCl, NaBr, NaNO 3 and Na 2 SO 4 ) leads to a decrease in the rate followed by an increase and it is found that tightly bound/incorporated anions are most effective.

Occupational Disease and Public Health Concerns of Migrant Construction Workers: A Social Epidemiological Study in Western Uttar Pradesh

The unorganised workers in the construction industry face several health hazards. The situation is doubly critical for the migrant construction workers (MCWs) due to congruence of their poor living and work environment. This is a cross-sectional study based on social epidemiological perspective. It studies the occupational disease, treatment patterns and other public health concerns of MCWs in urban spaces of western Uttar Pradesh. It uses semi-structured interview schedule and ethnographic observation during the fieldwork. The multi-stage cluster sampling is used to identify the required samples. Findings reveal that self-reported case of injury and disease among the MCWs in last one year is 35 per cent and 70 per cent, respectively. The public health facilities are missing in most of the construction sites. The migratory condition, narrow and unhygienic living space and lack of basic health facilities increase the burden of occupational diseases manifold on the migrant workers. Policy corrections are required not only for improving the conditions of migrant workers but also for removing disparities in economic and social development among the regions and states which will regulate the magnitude and direction of unproductive migration.

Correlation of age and gender with different histological subtypes of primary lung cancer

Background: Histological subtypes of lung carcinoma vary between gender and age groups. Younger age group has more predilections for adenocarcinoma (ACC) while squamous cell carcinoma (SCC) is more common in older age group. Gender wise, ACC is more frequent among females as compare to males. Aim: Present study analysed the distribution of histological subtypes among different age groups (younger vs. older) and gender (male vs. females) to find out predominance of any particular subtype or a specific pattern relating to age and gender in Indian population. Materials and Methods: Data of 342 patients were retrospectively analysed in terms of age, gender and pathological diagnosis. The patients were grouped into two, younger age group (≤50 years) and older age group (>50 years). Results: There were 280 (81.87%) male and 62 (18.12%) female patients. Male:female ratio was 4:51. There were 134 patients (39.18%) in younger age group and 208 (60.81%) patients in older age group. Majority of the patients (272) were nonsmall cell lung carcinoma (NSCLC) (79.53%) while 70 patients had small cell lung carcinoma (20.46%). Out of 272 patients with NSCLC, 130 (38%), were SCC, 92 (26.90%) patients had ACC and rest 50 (14.61%) patients were of large cell lung carcinoma. No significant predilection for a particular histological subtype in younger and older age group was observed. In males SCC was the most common subtype (42.14%, P = 0.0014) and in females ACC was most frequent (48.38%, P = 0.0001). Conclusion: Squamous cell carcinoma in males, ACC in females and overall SCC is the most common histological subtype. No significant correlation with age was found.

Sustainable development, health and STDs: A study of tribal society of Rajasthan

Sustainable development is a three-fold concept including economic sustainability, social sustainability and environmental sustainability. Sustainable development belongs to the social and cultural avenues of life, too, and health is an indispensable component in it. Human beings are at the centre of concerns for sustainable development, and they are entitled to a healthy and productive life in harmony with nature. The goals of sustainable development can only be achieved in the absence of a high prevalence of debilitating diseases and proper management of health activities at the grassroots level. This study reveals that a good proportion of the tribal population is suffering from problems of sexually transmitted diseases (STDs). These STDs are causing severe damage to them, not only physiologically but also socially and economically. The consequences related to STDs are endless. The HIV/AIDS phenomenon has made it more dreadful. The situation is more horrible in the tribal context because of their comparative unawareness about health and related activities. Findings reveal that a complete treatment of such STDs among the tribal persons is not a regular phenomenon; hence, an untreated STD not only keeps on multiplying the symptoms and the complications within the carrier but also results in spreading the disease fast within the community. Thus, the relation between disease and health is simple-when disease sustains, health suffers. Sustainable development aims at just the opposite situation, in which health sustains and disease suffers (gets eradicated).

Potential role of bio-inoculants and organic matter for the management of root-knot nematode infesting chickpea

Abstract A pot experiment was conducted during 2013–14 to observe the potential role of some organics and bio-organics such as Calotropis procera, Glomus fasciculatum, and Azotobacter chroococcum on some growth attributes of chickpea and subsequently on the root-knot development caused by Meloidogyne incognita. Individual and conjoint treatments significantly enhanced the plant growth parameters as compared to unamended control. Physiological parameter such as chlorophyll content also exhibited significant improvement in all the treatments over non-amended control. The highest improvement in growth parameters of chickpea was observed in combined application of G. fasciculatum and A. chroococcum in pots amended with C. procera. Moreover, combined treatments of both bio-inoculants and C. procera markedly reduced the multiplication and reproduction rate of root-knot nematodes in terms of number of root galls and nematode population. Percent mycorrhization in terms of external and internal colonizations was increased significantly in plant amended with organic and bio-organics conjointly. The regression studies revealed significant relationship between number of galls and some plant growth variables. Present findings may promote organic-based farm products and eco-friendly management of M. incognita as this is a safer and cost-effective option.

Multinodular bilateral breast lesions diagnosed as primary breast lymphoma in a young lactating woman

Primary breast lymphoma (PBL) is a rare neoplasm that constitutes 0.4% of malignant breast lesions and 2% of extranodal lymphomas. It is seldom distinguished preoperatively from other common forms of breast cancer. Here, we report a case of a 30-year-old woman (para 3, gravida 0) who presented with multiple bilateral nodular swellings of the breast for 2-months duration, followed by bilateral axillary lymphadenopathy after 15 days, along with low-grade fever, and generalized weakness. On examination, she was found to have multiple firm nodular mass involving both the right and the left breast, along with multiple, bilateral, matted, axillary lymph nodes. A clinical diagnosis of bilateral breast carcinoma with axillary metastasis was made. Fine needle aspiration cytology of both the breast and axillary lymph node revealed monomorphic population of scattered lymphoid cells with moderate anisonucleosis and one to two prominent nucleoli. A cytological diagnosis of PBL was made, which was subsequently confirmed with histopathology and immunohistochemistry for leukocyte common antigen and CD20. Because PBLs are uncommon malignant lesions and they usually do not have characteristic clinical and imaging findings, fine needle aspiration cytology proves to be a simple, rapid, reliable, and cost-effective procedure for successful diagnosis of PBL.

Psoas abscess: a rare metastatic presentation of asymptomatic carcinoma of the cervix

Abstract Isolated metastasis to the iliopsoas muscle is rare and is often misdiagnosed as psoas abcess, especially when it is the only presenting feature in the absence of a known primary tumour. A 52-year-old woman presented to us with a clinicoradiological diagnosis of psoas abscess. Initially, the patient was managed as a case of tubercular psoas abscess. However, later on, when the disease had not responded to antitubercular therapy, a cytological examination of aspirated material was performed, which confirmed it as being malignant in origin. While searching for primary malignancy, a small growth on the cervix was noticed. A biopsy and histopathological examination confirmed the diagnosis of squamous cell carcinoma of the cervix. A final diagnosis of squamous cell carcinoma of the cervix with isolated iliopsoas muscle metastasis was proposed. This case highlights an unusual site of metastasis in an asymptomatic primary tumour which was diagnosed retrospectively.