Quantitative and qualitative analysis of metallic ion release of orthodontic brackets in three different pH conditions - An invitro study.

Background: Fluoridated mouth rinses improve anti-cariogenic environment but decrease oral pH below critical value, affecting orthodontic bracket surface topography and causing corrosive changes over prolonged use. This invitro study aimed to quantitatively and qualitatively assess the surface topography and metallic ion release of the stainless steel (SS) brackets at varying acidic and alkaline pH. Materials and methods: Forty unused SS brackets were divided into four groups (Group A, B, C, D) and immersed for 48- hours in solutions of artificial saliva and sodium fluoride (0.2 %) mouth rinse at varying pH of 5.5,6.7,7 and 8. The surface morphologic changes were analyzed under scanning electron microscope (SEM) at 50×, 150×, and 500× magnification. The changes in slot area were scored using the customized scale. The Energy Dispersive Xray Spectroscopy Analysis (EDAX) was used to estimate the probed elements' atomic and weight percentage. Results: The mean score of the scale was 3.4 for the brackets immersed in the acidic solution which was statistically significant (p = 0.00)and for alkaline and neutral solutions (p = 0.00). Chromium was found to be significantly higher in the alkaline solution (p = 0.016) followed by the neutral solution. Carbon was found excess in acidic solution than the neutral and alkaline solution. Conclusion: Quantitative and qualitative analysis of the ion release in stainless steel brackets using SEM and EDAX revealed the corrosive effect of fluoride ion causing maximum surface changes in acidic medium and chromium release in alkaline pH.

Factors Affecting Biochemical and Echocardiographic Indices in Type 2 Diabetes Mellitus Patients Without Overt Symptoms of Heart Failure: A Cross-Sectional Study.

Introduction Diabetes is a known risk factor for heart failure (HF), and HF often manifests as a common cardiovascular event in people with type-2 diabetes mellitus (T2DM). Once HF is present, diabetes presents an especially adverse prognosis for subsequent morbidity and mortality. Brain natriuretic peptide (BNP) and n-terminal ProBNP (NT-proBNP) are used as diagnostic biomarkers for HF that are secreted by the ventricles in response to increased myocardial wall stress. If we could unmask some clinical and routine laboratory parameters affecting BNP and ejection fraction (EF), we can predict impending HF and take measures to prevent it. The current study was conducted to investigate the factors affecting BNP and EF for detecting potential HF in T2DM patients who do not exhibit overt HF symptoms. Materials and methods The present cross-sectional study was performed after obtaining ethical clearance from the Institutional Ethics Committee. T2DM patients consulting the Medicine Outpatient Department (OPD) of BRD Medical College Gorakhpur during a two-month period (from 20 July 2023 to 19 September 2023) with age >40 years and duration of T2DM >10 years. Multistage random sampling was done to recruit study participants, and 308 patients participated in the study. Informed consent was obtained from the recruited participants. The chi-square or Fisher's exact test (whichever was applicable) was used to explore the association between categorical variables. Correlation statistics were calculated using Spearman correlation among the NT-proBNP, EF, and other relevant variables. The Statistical Package for Social Sciences (SPSS) (version 21; IBM SPSS Statistics for Windows, Armonk, NY) was used for the analysis, and a two-sided p-value of < 0.05 was considered significant. Results Three hundred and eight diabetic patients satisfying inclusion and exclusion criteria were enrolled as study participants and completed the study. The mean age of the total study subjects was 60.82 ± 9.23 years. There were 161 (52.3%) male and 147 (47.7%) female participants, and about half (153/308, 49.7%) of the participants belonged to the age group 40-60 years. There was a statistically significant association (p = 0.01) between NT-proBNP and glycated hemoglobin. Statistically highly significant (p < 0.001) associations were found between NT-proBNP with duration of T2DM and EF. There was a strong negative correlation (correlation coefficient = -0.743) between EF and NT-proBNP, and this correlation was statistically highly significant with a p-value < 0.001. Conclusion Elevated NT-proBNP levels and impaired EF were found in a significant proportion of these patients, indicating an increased risk of cardiovascular complications. This study highlights a significant association between NT-proBNP and EF in patients with T2DM in those without overt heart failure symptoms. Furthermore, longer T2DM duration and higher HbA1c levels were found to be associated with elevated NT-proBNP levels, while longer T2DM duration and elevated NT-proBNP were linked to lower EF. These findings have important clinical implications, as they suggest that monitoring NT-proBNP levels in patients with T2DM without clinical features of overt heart failure may help identify those at risk for decreased EF and potentially prevent heart failure.

Langerhans cell histiocytosis of thyroid: Case report with review of literature.

Langerhans cell histiocytosis (LCH) is a rare monoclonal disease of antigen presenting cells. Involvement of thyroid gland by LCH is exceedingly rare. Herein, we present a case of LCH involving the thyroid in a 38-year-old woman. Our patient presented clinically as a case of primary thyroid neoplasm. Presence of elongated, epithelioid neoplastic cells with grooved nuclei along with presence of background eosinophils were seen on fine-needle aspiration cytology (FNAC) and histopathology. Positive staining for CD1a and S100 immunohistochemistry confirmed the diagnosis of LCH. Patient was given combination chemotherapy and has responded well to the same without any complaints for last 6 months. With this report, our goal is to expand awareness of this rare tumor in the thyroid. Consideration at the time of FNAC and its correct diagnosis on subsequent excision is imperative for patient management.

Pulmonary inflammatory myofibroblastic tumor coexisting with lymphangitis carcinomatosis: Mimicking metastatic papillary thyroid carcinoma with nodular fasciitis-like stroma.

Inflammatory myofibroblastic tumors (IMTs) are uncommon; intermediate grade soft tissue tumors occurring in young individuals with an uncertain behaviour. The incidence of pulmonary lymphangitis carcinomatosis (PLC) is around 6-8% of all pulmonary metastases. However, PLC due to papillary thyroid carcinoma (PTC) is very uncommon. We present a case of a 26-year-old male, who presented with a solitary left lung nodule on radiological scans. There was also a past history of thyroid surgery done two years back for PTC. Histology revealed a soft tissue tumor reminiscent of IMT. The periphery of the IMT nodule showed metastatic PTC in the form of extensive PLC. In view of this unusual histology, a diagnosis of PTC with nodular fasciitis-like stroma (PTC-NFS) was initially considered. However, molecular studies for anaplastic lymphoma kinase (ALK) gene rearrangement confirmed the diagnosis of IMT. This case highlights the unusual occurrence of tumor-to-tumor metastasis causing diagnostic challenges and also the importance of molecular testing.

Familial Gigantiform Cementoma with Calcium Steal Phenomenon and Social Stigma: A Case Report with Review of Literature.

Cemento-ossifying fibromas are benign fibro-osseous lesions characterized by deposition of cementum and fibrous tissue. Familial gigantiform cementoma (FGC) is an exceeding rare and distinct subtype of cemento-osseous-fibrous lesion. We hereby present a case of FGC in a young boy who was left to die due to the social stigma caused by the massive bony growth in the upper and lower jaw. The patient was somehow rescued by a non-governmental organization and underwent his surgical management at our hospital. On family screening, the mother also had similar smaller asymptomatic lesions in the jaw, but she refused further investigations and treatment. FGC is frequently associated with "calcium-steal phenomenon," which was also seen in our patient. Family screening is therefore necessary to identify asymptomatic patients in the family and follow them up with radiology and whole body dual-energy absorptiometry scans.

Eosinophilic solid cystic renal cell carcinoma: A series of 3 cases elucidating the spectrum of morphological and clinical features of an emerging new entity.

Eosinophilic solid cystic renal cell carcinoma (ESC-RCC) is a recently described entity, which demonstrates distinct clinical, pathological and molecular features. We present a series of three cases, the first to be reported from the Indian subcontinent. All three patients were over 50 years of age; and presented with a large kidney mass. One patient had a locally advanced disease while the other two presented with metastases. Microscopic examination revealed a tumor displaying solid-cystic and/or papillary areas composed of clear as well as eosinophilic cells in all three cases. On immunohistochemistry, all the three cases showed a unique CK20+/α-methyl-acyl-CoA-racemase + immunophenotype. Melan-A was focally positive in Case 2. Cytokeratin 7 was focally but strongly positive in Case 3. The two patients with metastatic disease were diagnosed on core biopsies and were advised oral tyrosine kinase inhibitor therapy. The third patient underwent upfront radical nephrectomy. Due to its peculiar morphology and immunoprofile, the diagnosis of ESC-RCC can be confidently made even on a core biopsy. Most cases reported till date had an indolent course. The metastatic presentation in two of our patients emphasizes the need to gather further evidence to ascertain the biological behavior of this emerging entity.

Gastrointestinal stromal tumor presenting with lower urinary tract symptoms - A series of five cases with unusual clinical presentation.

Spindle cell tumors of the prostate are very uncommon and the majority involve the prostate secondarily from adjacent organs. Gastrointestinal stromal tumors (GISTs) are specific C-kit (CD 117) expressing mesenchymal tumors occurring in the gastrointestinal tract, commonly in the stomach and intestine; however, it is seldom seen involving the prostate. Although primary prostatic GISTs have been described, majority of them are secondary involvement from rectal GIST. The patient usually presents with urinary tract symptoms or prostate enlargement simulating a prostatic neoplasm. GIST as a differential diagnosis for prostatic mass is never thought of. We present a series of five cases of GIST arising from/involving the prostate mimicking a primary prostatic malignancy and the challenges associated with them for diagnosis and treatment.

Overexpression and purification of folded domain of prostate cancer related proteins MSMB and PSA.

Overexpression of domains of a human protein using recombinant DNA technology has been challenging because individual domains intend to accumulate as non-soluble aggregate when expressed separately. Studies on identifying right sequences for a domain to be able to fold independently may help understand the folding pattern and underlying protein-engineering events to isolate the functional domains of a protein. In this report, individual domains of prostate cancer related biomarkers; MSMB and PSA were overexpressed in bacterial system and purified in their folded forms using affinity chromatography. The western blotting experiment using domain specific antibodies further confirmed these proteins. The designed nucleotide sequences domains were truncated using fold index software and folding were predicted by phyre2 and I-TASSER software. Other parameters were optimized for their overexpression and purification using Co-NTA affinity chromatography. Purified domains of each protein showed secondary structures such as α + ß type for PSA, α/ß and ß type for the each domains of PSA and MSMB respectively. This is the first report on producing PSA and MSMB individual domains in functional folded forms. This study may help produce the folded domain of many such proteins to be used for better diagnostic purpose.

Antimicrobial peptide (Cn-AMP2) from liquid endosperm of Cocos nucifera forms amyloid-like fibrillar structure.

Cn-AMP2 is an antimicrobial peptide derived from liquid endosperm of coconut (Cocos nucifera). It consists of 11 amino acid residues and predicted to have high propensity for ß-sheet formation that disposes this peptide to be amyloidogenic. In the present study, we have examined the amyloidogenic propensities of Cn-AMP2 in silico and then tested the predictions under in vitro conditions. The in silico study revealed that the peptide possesses high amyloidogenic propensity comparable with Aß. Upon solubilisation and agitation in aqueous buffer, Cn-AMP2 forms visible aggregates that display bathochromic shift in the Congo red absorbance spectra, strong increase in thioflavin T fluorescence and fibrillar morphology under transmission electron microscopy. All these properties are typical of an amyloid fibril derived from various proteins/peptides including Aß.

Natural antioxidant biomolecules promises future nanomedicine based therapy for cataract.

Cataract is an eye disease of major human concern and its prevention is important to control the global incidences of blindness. The emergence of cataract in the eye lens by strong UV radiation and growing pollution could be effectively reduced by natural antioxidant biomolecules such as flavonoids, phenolic acids, carotenoids and vitamins. This goal can be achieved either by direct external use of antioxidant biomolecules in the form of topical application as an eye drops, food supplements or through nanobiotechnology based formulation without any side effects. In this manuscript, we have discussed the mechanisms of cataract formation and the preventive role of different classes of natural antioxidant biomolecules. Further, role of nanobiotechnology to enhance therapeutic potential of these natural antioxidant molecules by enhancing solubility, stability, bioavailability and sustained release has been briefly discussed.

Development of stevioside Pluronic-F-68 copolymer based PLA-nanoparticles as an antidiabetic nanomedicine.

Stevioside (FDA approved nontoxic natural non-caloric sweetener) has been reported to have very good antidiabetic potential but its use as therapeutic drug is restricted in human due to its deprived intestinal absorption and poor bioavailability. We have nano-bioconjugated this molecule on biodegradable Pluronic-F-68 copolymer based PLA nanoparticles by nanoprecipitation method (spherical, size range 110-130 nm) to overcome deprived intestinal absorption and to enhance the bioavailability. The drug loading calculated by the standard calibrated HPLC was 16.32±4% (w/w). The in vitro release study showed the initial burst followed by the sustained release. The half release and complete release were observed on 25±4 h and 200±10 h respectively. This newly formulated nanostevioside showed very high potential to be used as antidiabetic nanomedicine for safe and effective use in vivo.

Development of antidiabetic nanomedicine from stevioside.

Stevioside, a non-caloric sweetener has huge therapeutic potential as an antidiabetic biomolecule. Stevioside nano-bioconjugated on PEG-PLA nanoparticles of size 150-170 nm showed the initial burst phase followed by the slow controlled release of 2 h and 21 days respectively.

Biodegradable polymeric nanoparticles based drug delivery systems.

Biodegradable nanoparticles have been used frequently as drug delivery vehicles due to its grand bioavailability, better encapsulation, control release and less toxic properties. Various nanoparticulate systems, general synthesis and encapsulation process, control release and improvement of therapeutic value of nanoencapsulated drugs are covered in this review. We have highlighted the impact of nanoencapsulation of various disease related drugs on biodegradable nanoparticles such as PLGA, PLA, chitosan, gelatin, polycaprolactone and poly-alkyl-cyanoacrylates.

Physiological changes and molluscicidal effects of crude latex and Milin on Biomphalaria glabrata.

Euphorbian latex is commonly used as molluscicides and the Euphorbia milii latex was reported as most powerful molluscicidal agents. The physiological and lethal effects of the latex components of Euphorbia milii, on the intermediate host Biomphalaria spp., of the human liver parasite Schistosoma mansoni were described in this study. The standard methodologies for testing plant derived molluscicides formulated by World Health Organisation (WHO) were followed with some modifications. The young specimen of fresh water snails showed altered physiological and physical response towards latex components. The working concentration of non-proteinaceous fraction (up to 0.1%) of the latex reduced the active physiological behaviour but was non-lethal to young specimen of snails. However, proteinaceous fractions (0.1mg/l) of the latex were found lethal to snail population, and lethality was enhanced with small amount of the non-proteinaceous fraction (0.01%) of the latex. Milin, a serine protease(up to 0.1mg/l), isolated from the latex of Euphorbia milii significantly reduced the growth and feeding activity but was not lethal to young specimen of snails. With an addition of 0.01% of non-proteinaceous fractions to Milin, lethality result was similar to that of crude latex. Milin is likely to be responsible for alteration of normal physiological functions and lethality of snails, thus it may be used as a molluscicide to control transmission of the endemic disease schistosomiasis.

A novel serine protease cryptolepain from Cryptolepis buchanani: purification and biochemical characterization.

A novel protease is purified to homogeneity from the latex of a medicinally important plant Cryptolepis buchanani of family Apocynaceae (formerly Asclepiadaceae). The enzyme named cryptolepain has a molecular mass of 50.5 kDa. The isoelectric point and extinction coefficient (epsilon280nm1%) are 6.0 and 26.4, respectively. Cryptolepain contains 15 tryptophans, 41 tyrosines, and eight cysteine residues forming four disulfide bridges. The detectable carbohydrate moiety in the enzyme was found to be 6-7%. Cryptolepain hydrolyzes denatured natural substrates like casein, azocasein, and azoalbumin with high specific activity. The protease is exclusively inhibited by serine protease inhibitors phenylmethansulfonyl fluoride and diisopropyl fluorophosphate. Hydrolysis of azoalbumin by the cryptolepain is optimal in the pH range of 8-10 and temperatures of 65-75 degrees C. The enzyme shows high stability against pH (2.5-11.5), temperature (up to 80 degrees C), and chemical denaturants. The Km value of the enzyme was found to be 10 microM with azocasein as the substrate. The N-terminal sequence of cryptolepain is unique and shows only little homology to other known serine proteases, which makes this enzyme an ideal candidate for our ongoing biochemical and structure-function investigations of proteases. Easy availability of the latex and simple purification procedures make the enzyme a good system for exploring the biophysical chemistry of serine proteases as well as applications in the food industry.

Highly stable glycosylated serine protease from the medicinal plant Euphorbia milii.

A serine protease, named as "Milin" was purified to homogeneity from the latex of Euphorbia milii, a medicinal plant of Euphorbiaceae family. The molecular mass (SDS-PAGE), optimum pH and temperature of the enzyme were 51kDa, pH 8.0 and 60 degrees C, respectively. Milin retains full proteolytic activity over a wide range of pH (5.5-12) and temperature (up to 65 degrees C) with casein and azoalbumin as substrates. The activity of milin is inhibited by serine proteases inhibitors like PMSF, APMSF and DFP, but not by any other protease inhibitors such as E-64 and PCMB. Like the other serine proteases from the genus Euphorbia, the activity of milin was not inhibited by the proteinaceous inhibitor soyabean trypsin inhibitor (SBTI) even at very high concentrations that is naturally present in plants. The specific extinction coefficient (epsilon(280 nm)(1%)), molar extinction coefficient (a(m)) and isoelectric point of the enzyme were found to be 29, 152,500 M(-1) cm(-1) and pH 7.2, respectively. The enzyme is a glycoprotein with detectable carbohydrate moiety (7-8%) in its constitution, which is essential for the activity. The numbers of tryptophan, tyrosine and cysteine residues in the sequence of milin were estimated chemically and are 23, 14 and 14, respectively. Of the 14-cysteine residues, 12 constituted 6-disulfide linkages while two are free cysteines. The N-terminal sequence (first 12 amino acid residues) was determined and does not match with any sequence of known plant serine proteases. Perturbation studies by temperature, pH and chaotropes of the enzyme also reveal its high stability as seen by CD, fluorescence and proteolytic activity. Thus, this serine protease may have potential applications in food industry.