Synthesis, molecular docking, analgesic, anti-inflammatory, and ulcerogenic evaluation of thiophene-pyrazole candidates as COX, 5-LOX, and TNF-α inhibitors.

The thiophene bearing pyrazole derivatives (7a-j) were synthesized and examined for their in vitro cyclooxygenase, 5-lipoxygenase, and tumour inducing factor-α inhibitory activities followed by the in vivo analgesic, anti-inflammatory, and ulcerogenic evaluations. The synthesized series (7a-j) were characterized using 1H NMR, 13C NMR, FT-IR, and mass spectral analysis. Initially, the compounds (7a-j) were evaluated for their in vitro cyclooxygenase, 5-lipoxygenase, and tumour inducing factor-α inhibitory activities and the compound (7f) with two phenyl substituents in the pyrazole ring and chloro substituent in the thiophene ring and the compound (7g) with two phenyl substituents in the pyrazole ring and bromo substituent in the thiophene ring were observed as potent compounds among the series. The compounds (7f and 7g) with effective in vitro potentials were further analyzed for analgesic, anti-inflammatory, and ulcerogenic evaluations. Also, to ascertain the binding affinities of compounds (7a-j), docking assessments were carried out and the ligand (7f) with the highest binding affinity was docked to know the interactions of the ligand with amino acids of target proteins.

From sugar binders to diabetes fighters: the lectin saga of antihyperglycemic activity through systematic review and meta-analysis.

Introduction: Lectins are carbohydrate-binding proteins that are extremely selective for sugar groups in the other molecules. As a result, they perform a variety of roles in biological processes involving cell, carbohydrate, and protein recognition at the cellular and molecular levels. Because lectins can bind to carbohydrates, they may play a role in determining the rate of carbohydrate digestion. They also bind to some proteins involved in diabetes mellitus (DM) pathophysiology. The present review aims to summarize the efficiency of lectins from different sources as potential antihyperglycemic agents. Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were employed for the drafting. In this regard, published scientific articles on the effects of different lectins on blood glucose (BG), glucose tolerance, hormonal effects, carbohydrate-digesting enzymes, oxidative stress, and insulin production process were collected from reputed journals using electronic databases. Furthermore, the toxicity effects of lectins from different sources were collected. A specific keyword search was completed to collect numerous articles with unique experimental designs and significant results. This was followed by the selection of the requisite articles based on the criteria designed by the authors. Data extraction was based on the common research elements included in the articles. Results and Discussion: Of 13 identified studies, 11 studies were considered after double screening based on the inclusion criteria. All 11 pharmacological investigations were considered for review. Subsequent studies reflected on the pharmacological properties of lectins on the levels of BG, oxidative stress, ß-cell proliferation, insulin resistance, inhibition of carbohydrate digesting enzymes, body weight, food and water intake, lipid profile, and other parameters. This review highlights lectins as potential anti-diabetic agents. Conclusion: However, due to limited research, systematic evaluation is recommended for their development and promotion as effective potential antihyperglycemic agents. The clinical efficacy and safety of lectins against diabetes mellitus must also be evaluated.

Formulary availability and regulatory barriers to accessibility of opioids for cancer pain in India: a report from the Global Opioid Policy Initiative (GOPI).

India is the world's largest democracy with control of opioids divided between the national and state governments. While the global consumption of opioids has increased, the consumption has not increased at the same rate. This is the first comprehensive study of opioid availability and accessibility for cancer patients in India. Data are reported on the availability and accessibility of opioids for the management of cancer pain in 24 of the states that make up India and the Administrative area around Delhi. About 1061 million of the nation's 1189 million people (89%) are covered by this survey. Without exception, opioid availability continues to be low throughout all of India. Even when opioids are on formulary, they are often unavailable. Access is significantly impaired by widespread over-regulation that continues to be pervasive across the nation.

Protocol to identify multiple protein targets and therapeutic compounds using an in silico polypharmacological approach.

Polypharmacology aids in the identification of multiple protein targets involved in disease pathology and selecting appropriate therapeutic compounds interacting with protein targets. Here, we present a protocol to identify the targets involved in obesity-linked diabetes and suitable phytocompounds to bind with the identified target. We describe steps to install and use softwares for identifying several protein targets by linking multiple diseases. This protocol allows the use of therapeutic compounds of both phytochemical and synthetic origins. For complete details on the use and execution of this protocol, please refer to Martiz et al.,1 and Maradesha et al.2.

Effect of dermatan sulfate on the indentation and tensile properties of articular cartilage.

OBJECTIVE: This paper examines the hypothesis that the dermatan sulfate (DS) chain on decorin is a load carrying element in cartilage and that its damage or removal will alter the material properties. METHODS: To test this hypothesis, indentation and tensile testing of cartilage from bovine patella were performed before and after digestion with chondroitinase B (cB). Removal of significant amounts of DS by cB digestion was verified by Western blot analysis of proteoglycans extracted from whole and sectioned specimens. Specimens (control and treated) were subjected to a series of step-hold displacements. Elastic modulus during the step rise (rapid modulus) and at equilibrium (equilibrium modulus), and the relaxation function during each step was measured for test (cB and buffer) and control (buffer alone) conditions. RESULTS: cB had no effect on any of the viscoelastic mechanical properties measured, either in indentation or tension. CONCLUSION: Removing or damaging approximately 50% of the DS had no effect on the mechanical properties, strongly suggesting that DS either carries very low load or no load.

Results of 87 cases of intraocular lens implantation at the front of the whole capsular bag.

To prevent or delay Elschnig pearl formation, we performed an unusual surgical technique on 87 patients: intraocular lens implantation at the front of the whole capsular bag. We tried to obtain tight adhesion between the anterior and posterior capsules so the lens epithelial cells could not proliferate and form Elschnig pearls. In fact, the patients exhibited no Elschnig pearls or Soemmering's ring, but developed large anterior capsular folds and a multilayer cell membrane between both capsules after two (three cases), six (19 cases), and 12 months (14 cases). This led to a decrease in visual acuity, and a Nd:YAG laser anterior and posterior capsulotomy was required in most cases (83%). Several months later, these eyes developed enormous Elschnig pearls emanating centrifugally from the laser opening, strongly suggesting that lens epithelial cells require aqueous humor for Elschnig pearl transformation. Since it is not yet possible to obtain perfect adhesion between anterior and posterior capsules, our results confirm the need to remove the anterior capsule after extracapsular cataract extraction.

A composites theory predicts the dependence of stiffness of cartilage culture tissues on collagen volume fraction.

The tensile stiffness of tissue grown from chondrocyte culture was both measured experimentally and predicted using a composites model theory relating tissue microstructure to macroscopic material stiffness. The tissue was altered by several treatment protocols to provide a wide range of collagen fibril volume fraction (0.015-0.15). The rate of change of tissue modulus with change in collagen volume fraction predicted by the theory was within 14% of the slope of the linear fit through the experimental data, without the use of fitting parameters for the theoretical value of the slope. Use of the model to simulate cytokine mediated tissue digestion suggests that the action of IL-1beta and retinoic acid is mainly removal of proteoglycans and some removal of collagen. The model also indicates that the matrix and collagen remaining in the tissue has the same elastic properties as the untreated tissue, and is not damaged due to the alteration. Young's modulus of the collagen fibrils is predicted to be 120 MPa, a value in the range of previous studies. This value is dependent mainly on the matrix modulus and collagen fibril volume fraction and not on Poisson's ratio of either matrix or fibril. Poisson's ratio of the tissue depends primarily on the Poisson's ratio of the matrix.

Atypical carcinoid of larynx: a case study and a brief review.

Atypical Carcinoids, Malignancy arising from neuroendocrine cells are among the non-Epidermoid cancers of larynx.The present study reports an interesting and rare case of atypical carcinoid of larynx. An 85-year-old male patient presented with a history of dysphagia.On clinical examination, a provisional diagnosis of cyst larynx was made. But during surgery, the Diagnosis had to be reviewed as benign lesion of the larynx. Histopathological diagnosis was atypical carcinoid. The present study discusses the unusual presentation and unusual clinical diagnosis of these neuroendocrine neoplasms of larynx.

[Congenital glaucoma of dominant autosomal transmission apropos of a family. Management]. / Glaucome congénital à transmission autosomique dominante. A propos d'une famille. Conduite à tenir.

The study of three consecutive generations of patients having a late revelation congenital glaucoma, make us discuss about several kinds of inheritance of the congenital glaucoma, especially the dominant autosomal form, well adapted to a genetic counsel which is necessary in all the cases, because of the severity of this disease.

Evaluation of fracture toughness of cartilage by micropenetration.

Failure properties of cartilage are important in injury repair and disease, but few methods exist for measuring these properties, especially in small animals. To meet this need, a new indentation/penetration method for measuring fracture toughness of cartilage is proposed. During indentation, a conical tip is displaced into the surface of the cartilage, causing first a non-penetrating indentation, and then a penetration into the tissue. The method assumes that tissue penetration occurs during periods of "rapid work", which are identified from a curve of work rate vs. time. Total penetration depth is determined by summing the displacement during these periods. Fracture work is the work that occurs during "rapid work", or penetration, and fracture toughness defined as the fracture work divided by one-half the penetrated surface area of the indenting tip. The method was validated by indentation testing of bovine cartilage. Penetrating indentations with a conical tip were performed in bovine patellar cartilage and depth of penetration and fracture toughness predicted. For comparison with the indentation data, depth of penetration was measured in histological sections. These measurements agreed well with the predicted depth. Predicted fracture toughness also agreed with values measured via a macroscopic test. This newly described method has promise as a general method for measuring fracture toughness in cartilage, particularly in small animals, since penetrating tips with small tip radius can be manufactured and penetration may be accomplished in cartilage of minimal thickness.

Effects of electrolytic lesions of the superior olivary complex and trapezoid body on brainstem auditory-evoked potentials in the guinea pig. I. Vertex-tragus recordings.

Brainstem auditory-evoked potentials (BAEP) were recorded between vertex and tragus in 22 guinea pigs, after destruction of the contralateral ear in order to produce monaural stimulation. Stimuli employed were 100 dB SPL clicks and tone bursts. Normative recordings showed five positive peaks, P1-P5 and four negative peaks, N1-N4. Electrolytic lesions were then made to the superior olivary complex (SOC) ipsilateral to the stimulation (6 animals), contralateral to the stimulation (8 animals), and trapezoid body (TB) (8 animals). In each group a statistical analysis of the results (amplitudes and latencies) was made (paired t test). After lesions to the ipsilateral SOC, there was an increase in the amplitude of P1 and a decrease in P3. After lesions to the contralateral SOC, there was a larger decrease in P3, which disappeared in 2 guinea pigs which had a large lesion involving many TB fibers. After TB lesions, there was a decrease in the P2-N2 composite wave, disappearance of P3, a decrease in P4, and an increase in the latency of P1 and P1-P2 and P2-P4 intervals. After ipsilateral SOC lesions, which certainly involved the uncrossed olivocochlear efferent tract, the increase in P1 suggested a disinhibition of the efferent fibers. The large decrease or the loss of P3 after TB lesions and SOC lesions involving many TB fibers suggested that P3 could be generated by the contralateral part of the TB fibers, in the vicinity of the contralateral SOC. These data are in agreement with the predominance of fiber tracts in the generation of BAEP.

Effects of electrolytic lesions of the superior olivary complex and trapezoid body on brainstem auditory-evoked potentials in the guinea pig. II. Three-channel Lissajous' trajectory analysis.

Brainstem auditory-evoked potentials (BAEP) were studied both with vertex (positive) - tragus (negative) derivation and three-channel Lissajous' trajectory (3-CLT) planar analysis in guinea pigs (GP) after destruction of the ipsilateral superior olivary complex (SOC) (6 GP), contralateral SOC (8 GP) referred to the stimulation side, and trapezoid body (TB) in the sagittal line (8 GP). The size of the lesion was evaluated on histological examination. The right ear was locally destroyed with aminoside instillation. The left ear was stimulated with unfiltered clicks and tone bursts of different frequencies at 100 dB SPL. Three questions were the basis of this study: (i) What are the effects of brainstem lesions on 3-CLT? (ii) Is there a relationship between planar segments and underlying sources? (iii) What is the generator of planar segment C (P3) in GP? 3-CLT analysis was made on plane A (corresponding to P1 on a vertex-tragus channel), plane B (N1-P2) and plane C (P3.) Plane C disappeared after TB lesions and remained after ipsi- and contralateral SOC destructions. However, plane C disappeared after extensive lesions to the contralateral SOC affecting the TB. Planes A and B were always observed whatever the lesion, with sometimes a modification of their orientation. A localized brainstem lesion induced a local modification of the three-dimensional trajectory. These data are in agreement with the assumption that some planes of 3-CLT reflect the activity of underlying generators. However, the loop which contains the planar segment is a better indicator of the global electrical activity of the source. Plane C (P3) would have a contralateral source which is probably not the SOC but the afferent curved fibers of the TB close to the contralateral SOC.