Antiangiogenic Therapeutic mRNA Delivery Using Lung-Selective Polymeric Nanomedicine for Lung Cancer Treatment.

Therapeutic antibodies that block vascular endothelial growth factor (VEGF) show clinical benefits in treating nonsmall cell lung cancers (NSCLCs) by inhibiting tumor angiogenesis. Nonetheless, the therapeutic effects of systemically administered anti-VEGF antibodies are often hindered in NSCLCs because of their limited distribution in the lungs and their adverse effects on normal tissues. These challenges can be overcome by delivering therapeutic antibodies in their mRNA form to lung endothelial cells, a primary target of VEGF-mediated pulmonary angiogenesis, to suppress the NSCLCs. In this study, we synthesized derivatives of poly(ß-amino esters) (PBAEs) and prepared nanoparticles to encapsulate the synthetic mRNA encoding bevacizumab, an anti-VEGF antibody used in the clinic. Optimization of nanoparticle formulations resulted in a selective lung transfection after intravenous administration. Notably, the optimized PBAE nanoparticles were distributed in lung endothelial cells, resulting in the secretion of bevacizumab. We analyzed the protein corona on the lung- and spleen-targeting nanoparticles using proteomics and found distinctive features potentially contributing to their organ-selectivity. Lastly, bevacizumab mRNA delivered by the lung-targeting PBAE nanoparticles more significantly inhibited tumor proliferation and angiogenesis than recombinant bevacizumab protein in orthotopic NSCLC mouse models, supporting the therapeutic potential of bevacizumab mRNA therapy and its selective delivery through lung-targeting nanoparticles. Our proof-of-principle results highlight the clinical benefits of nanoparticle-mediated mRNA therapy in anticancer antibody treatment in preclinical models.

The CryoPop study: Screening for high-grade cervical dysplasia in Karnataka, India.

OBJECTIVE: To describe our experience of screening with visual inspection with acetic acid (VIA) and colposcopy to identify women with high-grade precancerous cervical lesions who were candidates for cryotherapy. Women were screened to determine eligibility for a clinical trial testing the safety and efficacy of a new, simple and inexpensive cryotherapy device (CryoPop®) targeted for use in low and middle-income countries (LMICs). DESIGN: Prospective cohort study. SETTING: Primary and urban health centres in Belagavi, Hubballi and Vijayapur, India. POPULATION: Women in the age-group 30-49 years, premenopausal, with no prior hysterectomy and no known HIV infection were eligible for screening. METHODS: Visual inspection with acetic acid was performed on eligible women following informed consent. VIA-positive women were referred for colposcopy and biopsy. Biopsies were read by two pathologists independently, with a third pathologist acting as tie-breaker if needed. MAIN OUTCOME MEASURES: The primary outcome measures were the number/proportion of women screening positive by VIA and the number/proportion of those women screening VIA-positive found to have high-grade cervical lesions on biopsy (cervical intraepithelial neoplasia 2/3 [CIN 2/3]). Demographic variables were compared between women who screened VIA-positive and those who screened VIA-negative; a separate comparison of demographic and limited reproductive variables was performed between women who had CIN 2/3 on biopsy and those without CIN 2/3 on biopsy. Chi-square or Fisher's exact tests for categorical data and t-tests or analysis of variance for numeric data were used with all tests two-sided and performed at an alpha 0.05 level of statistical significance. RESULTS: A total of 9130 women were screened with VIA between 4 July 2020 and 31 March 2021. The mean age of all women screened was 37 years (standard deviation = 5.6 years) with 6073 of the women (66.5%) in the 30-39 year range. Only 1% of women reported prior cervical cancer screening. A total of 501 women (5.5%) were VIA-positive; of these, 401 women underwent colposcopy. Of those who had colposcopy, 17 (4.2%) had high-grade lesions on biopsy, an additional 164 (40.9%) had low-grade cervical lesions on biopsy or endocervical curettage and one woman (0.2%) was found to have invasive cancer. VIA-positive women were younger and had higher levels of education and income; however, women who were VIA-positive and found to have CIN 2/3 were older, were more likely to be housewives and had higher household income than those without CIN 2/3. CONCLUSION: Despite the COVID-19 pandemic, over 9100 women were screened with VIA for precancerous lesions. However, only 17 (4.2%) were found to have biopsy-proven high-grade cervical lesions, underscoring the subjective performance of VIA as a screening method. Given that this is significantly lower than rates reported in the literature, it is possible that the prevalence of high-grade lesions in this population was impacted by screening a younger and more rural population. This study demonstrates that screening is feasible in an organised fashion and can be scaled up rapidly. However, while inexpensive and allowing for same-day treatment, VIA may be too subjective and have insufficient accuracy clearly to identify lesions requiring treatment, particularly in low-prevalence and low-risk populations, calling into question its overall cost-effectiveness.

Evaluation of Her-2 protein in histologically tumor-free margins of oral squamous cell carcinoma: An immunohistochemical study.

Background: The status of the 5-year survival rate and loco-regional recurrence in oral squamous cell carcinoma (OSCC) has remained unchanged over the decades. Recent advances in oral cancer research have revealed that the presence of molecular alterations in histologically tumor-free margins of OSCC has a prognostic significance and can aid in designing therapeutic strategies. However, the literature on molecular studies on histologically tumor-free margins is scant, especially in the Indian population. Considering the prognostic implications of Her-2 in malignancies of the breast, ovary, and OSCC, we aimed to assess the expression of Her-2 protein in histologically tumor-free margins of OSCC and to establish correlation with clinico-pathological parameters. Methods: 4 µ m thick sections from formalin-fixed paraffin-embedded tissue blocks of 40 histologically tumor-free margins of OSCC affecting the buccal mucosa and/or lower gingiva-buccal sulcus and 40 normal oral mucosa samples were subjected to immunohistochemical analysis for the Her-2 antibody. The obtained data were analyzed statistically. Results: The mean ages in study and control groups were 49.83 years (SD ± 10.43) and 37.28 years (SD ± 8.61), respectively, with male predominance. Local recurrence was seen in 52.5% of patients. Follow-up data revealed that a total of 71.4% of patients succumbed to mortality and all of them had reported local recurrence. Overall, the presence of local recurrence and the status of survival showed a statistically significant association (p = 0.0001). All the samples in the study and control groups were negative for Her-2 immuno-expression. Conclusion: The study indicated the lack of Her-2 immuno-expression in histologically tumor-free margins of OSCC with several speculated explanations. As it is a preliminary study, further studies employing both immunohistochemistry (IHC) and gene amplification in histologically tumor-free margins of OSCC affecting different anatomical sites are warranted. This will aid in identifying the subset of patients that may benefit from targeted therapy.

Functional ligands for improving anticancer drug therapy: current status and applications to drug delivery systems.

Conventional chemotherapy lacking target selectivity often leads to severe side effects, limiting the effectiveness of chemotherapy. Therefore, drug delivery systems ensuring both selective drug release and efficient intracellular uptake at the target sites are highly demanded in chemotherapy to improve the quality of life of patients with low toxicity. One of the effective approaches for tumor-selective drug delivery is the adoption of functional ligands that can interact with specific receptors overexpressed in malignant cancer cells. Various functional ligands including folic acid, hyaluronic acid, transferrin, peptides, and antibodies, have been extensively explored to develop tumor-selective drug delivery systems. Furthermore, cell-penetrating peptides or ligands for tight junction opening are also actively pursued to improve the intracellular trafficking of anticancer drugs. Sometimes, multiple ligands with different roles are used in combination to enhance the cellular uptake as well as target selectivity of anticancer drugs. In this review, the current status of various functional ligands applicable to improve the effectiveness of cancer chemotherapy is overviewed with a focus on their roles, characteristics, and preclinical/clinical applications.

Impact of low-molecular-weight heparin in the treatment of moderately severe and severe acute pancreatitis; a randomized, single blind, phase 3 control trial.

INTRODUCTION: Acute pancreatitis is inflammation of pancreatic parenchyma which is an emergency condition. It is classified as mild, moderately severe, and severe categories. In severe acute pancreatitis, mortality is up to 10%-30%. Pancreatic abscess increases the mortality to 40%, and infected pancreatitis carries 100% mortality without surgical drainage. Anti-coagulant, anti-inflammatory and anti-protease activities of low-molecular-weight heparin are involved in preventing pancreatic necrosis and curbing the adverse outcomes of acute pancreatitis. AIM: To determine the effect of low-molecular-weight heparin on the outcome of moderately severe and severe acute pancreatitis. MATERIALS AND METHODOLOGY: Hospital based, single centre, randomized, single blind, phase 3 control trial. First 140 patients with moderately severe and severe acute pancreatitis admitted in hospital in the given period who met the inclusion and exclusion criteria were taken. 70 patients were placed in the control and the trial group each by simple randomization (closed envelope method). The control group received conventional treatment for pancreatitis & the trial group received 1mg/kg body weight Enoxaperin, subcutaneously, 12 hourly for seven days along with the conventional treatment. Progression of disease in Computed Tomography Severity Index and incidence of pancreatic necrosis were the main outcomes studied at the end of 7 days of treatment. RESULTS: 1386 acute abdomen cases were screened, of which 269 were diagnosed with acute pancreatitis. 147 patients with acute pancreatitis met the selection criteria and 7 were dropouts. Recruitment started on April 9, 2021 and closed on December 5, 2021. Computed Tomography Severity Index progressed in 22(31.40%) patients in control group and 6(8.6%) patients in the trial group and 18(25.71%) in the control group and 4(5.71%) in the trial group showed the presence of necrosis. The differences are significant (P value is 0.001 in each). No adverse events were seen. CONCLUSION: Use of low-molecular-weight heparin in early stage of moderately severe and severe acute pancreatitis significantly reduces the chance of disease progression and pancreatic necrosis.

A Study of Lipid Profile in Non-Diabetic Ischemic Stroke in Young Patients.

Cerebrovascular accident is the most important non communicable disease resulting in 2nd leading cause of death and 3rd leading cause of disability worldwide. Lipoproteins are considered as an independent risk factor for atherosclerosis. The atherogenecity of diabetics and non-diabetics are different. To study fasting serum lipid profile in patient with non-diabetic stroke and to determine significant correlation between them. MATERIAL: The prospective observational study was done in the Department of Medicine M.R Medical College between 1st October 2019-31th March 2021. Fasting serum lipid profile was done on 50 patients of non-diabetic ischemic stroke in young patients. OBSERVATION: In this study 62 %of patients had HDL<40 mg/dl, 42% had total cholesterol >200 mg/dl, 70 % of them had LDL cholesterol > 100 mg/dl and 44 % of patients had VLDL >30 mg/dl. In this study total cholesterol and LDL cholesterol were significantly associated with risk of stroke. CONCLUSION: This study showed significant association of total cholesterol and LDL cholesterol in non-diabetics with stroke. Dyslipidemia modifiable risk factor, routine screening with lipid profile and early initiation of treatment of lipid lowering drugs will reduce the incidence of ischemic stroke.

Recent advancements in lipid-mRNA nanoparticles as a treatment option for cancer immunotherapy.

Background: Cancer remains a serious health concern worldwide, and different approaches are being developed for its treatment. The strategy to use the immune system as an approach for treating cancer has recently gained momentum. Messenger RNA (mRNA) has been assessed as an up-and-coming resource for the evolution of advanced cancer immunotherapies over the past decades. However, degradation in extracellular compartments and during endosomal escape remain obstacles for efficient mRNA delivery and limit the therapeutic applications of this approach. Area covered: Lipid-based nanocarriers are gaining significant attention as non-viral mRNA vectors. Various lipid-based nanocarrier types have been developed to enhance the stability of mRNA molecules, facilitate their transfection, and ensure delivery to an intracellular compartment suitable for further processing. This review discusses the development of novel mRNA delivery systems using lipids for effective cancer immunotherapy. Expert opinion: mRNAs are superior to other biomolecules for developing therapeutic drugs and vaccines with multiple medical applications that are currently being explored by researchers in various biomedical fields. Lipid-based mRNA nanoparticles can improve the potency of the mRNA by enhancing its stability, enabling its cellular uptake, and facilitating its endosomal escape. Targetability of these therapeutics can be increased by conjugating their surface with the desired ligands or targeting agents. Lipid-mRNA nanoparticles are increasingly being incorporated in cancer immunotherapy applications, including vaccines, monoclonal antibodies, and chimeric antigen receptor T-cell treatment, and several such nanoparticles are being assessed in clinical trials. Further research that assesses key variables for transfection efficiency of lipid-mRNA nanoparticles will expedite the development of improved therapeutics.

Safety and efficacy of the new CryoPop® cryotherapy device for cervical dysplasia in low- and middle-income countries: study protocol for a multicenter open-label non-inferiority clinical trial with historical controls.

BACKGROUND: Cervical cancer is the fourth most common cancer in the world, affecting mainly women residing in low- and middle-income countries. Progression from a pre-invasive phase to that of an invasive phase generally takes years and provides a window of opportunity to screen for and treat precancerous lesions. METHODS: This study is being conducted at four sites in north Karnataka, India. Community sensitization activities have been organized in the study areas to create awareness among stakeholders, including elected representatives, physicians, health care workers, and potential participants. Organized community based as well as hospital-based screening is being conducted using visual inspection with acetic acid (VIA). Screen positive women are referred to respective study hospitals for colposcopy and directed biopsy. Participants with confirmed high-grade cervical dysplasia (high-grade squamous intraepithelial lesions or HSIL) who fit all other eligibility criteria will be recruited to the study and will receive cryotherapy using CryoPop®, an innovative new cryotherapy device. DISCUSSION: There is a need to develop an inexpensive, simple, and effective cryotherapy device for use by frontline health care providers at locations where screening and timely treatment can be given, accelerating access to cervical cancer prevention services and minimizing loss to follow-up of women with precancerous lesions who need treatment. TRIAL REGISTRATION: Clinical Trial Registry - India CTRI/2019/01/017289 ClinicalTrials.Gov number NCT04154644 . Registered on November 6, 2019.

Mapping QTL hotspots associated with weed competitive traits in backcross population derived from Oryza sativa L. and O. glaberrima Steud.

To improve grain yield under direct seeded and aerobic conditions, weed competitive ability of a rice genotype is a key desirable trait. Hence, understanding and dissecting weed competitive associated traits at both morphological and molecular level is important in developing weed competitive varieties. In the present investigation, the QTLs associated with weed competitive traits were identified in BC1F2:3 population derived from weed competitive accession of O. glaberrima (IRGC105187) and O. sativa cultivar IR64. The mapping population consisting of 144 segregating lines were phenotyped for 33 weed competitive associated traits under direct seeded condition. Genetic analysis of weed competitive traits carried out in BC1F2:3 population showed significant variation for the weed competitive traits and predominance of additive gene action. The population was genotyped with 81 genome wide SSR markers and a linkage map covering 1423 cM was constructed. Composite interval mapping analysis identified 72 QTLs linked to 33 weed competitive traits which were spread on the 11 chromosomes. Among 72 QTLs, 59 were found to be major QTLs (> 10% PVE). Of the 59 major QTLs, 38 had favourable allele contributed from the O. glaberrima parent. We also observed nine QTL hotspots for weed competitive traits (qWCA2a, qWCA2b, qWCA2c, qWCA3, qWCA5, qWCA7, qWCA8, qWCA9, and qWCA10) wherein several QTLs co-localised. Our study demonstrates O. glaberrima species as potential source for improvement for weed competitive traits in rice and identified QTLs hotspots associated with weed competitive traits.

Design of a Novel Theranostic Nanomedicine (III): Synthesis and Physicochemical Properties of Tumor-Targeting Cisplatin Conjugated to a Hydrophilic Polyphosphazene.

PURPOSE: A new theranostic nanomedicine involving anticancer-active cisplatin moiety was designed to study its tumor-targeting properties as well as its drug efficacy and toxicity. METHODS: A cisplatin carrier polymer was prepared by grafting equimolar polyethylene glycol of a molecular weight of 550 (PEG550) and aminoethanol to the poly(dichlorophosphazene) backbone. Cisplatin was conjugated to the carrier polymer using cis-aconitic acid as a linker. RESULTS: The cisplatin-loaded polyphosphazene, named "Polycisplatin" was found to be amphiphilic in aqueous solution and self-assembled into nanoparticles with an average particle size of 18.6 nm in diameter. The time-dependent organ distribution study of Cy5.5-labeled Polycisplatin in the A549-tumor-bearing mice exhibited a high tumor selectivity of Polycisplatin by EPR effect despite the relatively small particle size. In order to compare the in vivo efficacy of Polycisplatin and cisplatin, their xenograft trials were performed using nude mice against the human gastric cell line MKN-28. Polycisplatin exhibited slightly less tumor suppression effect compared with cisplatin at the same dose of 1.95 mg Pt/kg, which is the maximum tolerate dose of cisplatin, but at the higher double dose of 3.9 mg Pt/kg, Polycisplatin exhibited a little better efficacy than cisplatin. Furthermore, mice treated with cisplatin at the dose of 1.95 mg Pt/kg exhibited severe body weight decrease by about 25%, while mice treated with Polycisplatin did not show serious body weight decrease even at its double dose of 3.9 mg Pt/kg. Furthermore, kidney indicators including kidney index, BUN, and creatinine values measured displayed that Polycisplatin is much less nephrotoxic than cisplatin. CONCLUSION: Nanoparticular Polycisplatin was successfully prepared by conjugating cisplatin to a hydrophilic polyphosphazene carrier polymer using the acid-cleavable cis-aconitic acid. Polycisplatin nanoparticles exhibit excellent tumor-targeting properties by EPR effect. The xenograft trials exhibited excellent antitumor efficacy and reduced systemic toxicity of Polycisplatin.

Radiation biology of a serious tropical pigeon pea pest, Maruca vitrata (Fabricius) (Lepidoptera: Crambidae) and potential of radiation mediated 'inherited (F1) sterility technique' for the pest suppression.

Purpose: The impact of gamma radiation on the reproductive biology of the spotted pod borer, Maruca vitrata (Fabr.) (Lepidoptera: Crambidae) was ascertained to explore the potential of the radio-genetic 'Inherited (F1) Sterility' technique (modified Sterile Insect technique) to control this serious pigeonpea pest in India.Materials and methods: Radio-biological investigations involved dose-response studies, at a range of 100-250 Gy, with respect to radiation induced adverse effects on reproductive behavior in substerilized parent (P1) moths, inheritance of sterility and associated metamorphic disruption in F1 progeny. The reproductive competence of P1 male moths and their F1 progeny was evaluated by ascertaining the survival, mating success, sperm transfer and amphimixis of gametes from irradiated male parents and their F1 progeny. Daily ovipositional and egg fertility profile were evaluated as crucial parameters for simulation modeling for this radio-genetic technique.Results: Radiation-induced check in insemination rate and sterility in P1 and F1 generation had a positive correlation with gamma dose. The metamorphic adverse effects in F1 progeny of substerilized P1 males were influenced by P1 irradiation. A higher dose of 200 Gy that resulted in 21.1% fertility in parent cross (P1♂x N♀) could form only 14.4% F1 adults that were all malformed. A gamma dose of 150 Gy (administered to P1 males) could be considered as a suitable dose for F1 sterility, that induced 57.4% control of reproduction in parent generation, followed by 72-85% control of reproduction in F1 progeny involved in three crosses -F1♂xN♀, N♂xF1♀, F1♂xF1♀. Daily fertility profile of the eggs laid indicated a marked reduction on 4th day onwards during the ovipositional span in P1 and F1 generation. High degree of mating competitiveness value (CV) was noticed for 150 Gy irradiated male P1 moths (0.78-0.93), and their F1 male progeny (0.70-0.89), released in different sex ratios in the field cages having untreated moths. Reduced relative damage to the pigeon pea plants by the released F1 progeny in the field cages was observed in comparison to control.Conclusion: The present study indicated the potential use of a dose of 150 Gy to apply the 'F1 sterility' technique for parabiological suppression of the pigeon pea pod borer. The present findings and reproductive performance of the irradiated moths in F2 generation along with other compatible biorational pest control tactics (that are in progress), might help in formulating an effective integrated pest management module, including the F1 sterility technique as an integral component.

Annexin A2 and its downstream IL-6 and HB-EGF as secretory biomarkers in the differential diagnosis of Her-2 negative breast cancer.

Background AnnexinA2 (AnxA2) membrane deposition has a critical role in HB-EGF shedding as well as IL-6 secretion in breast cancer cells. This autocrine cycle has a major role in cancer cell proliferation, migration and metastasis. The objective of the study is to demonstrate annexinA2-mediated autocrine regulation via HB-EGF and IL-6 in Her-2 negative breast cancer progression. Methods Secretory annexinA2, HB-EGF and IL-6 were analysed in the peripheral blood sample of Her-2 negative ( n = 20) and positive breast cancer patients ( n = 16). Simultaneously, tissue expression was analysed by immunohistochemistry. The membrane deposition of these secretory ligands and their autocrine regulation was demonstrated using triple-negative breast cancer cell line model. Results Annexina2 and HB-EGF expression are inversely correlated with Her-2, whereas IL-6 expression is seen in both Her-2 negative and positive breast cancer cells. RNA interference studies and upregulation of annexinA2 proved that annexinA2 is the upstream of this autocrine pathway. Abundant soluble serum annexinA2 is secreted in Her-2 negative breast cancer (359.28 ± 63.73 ng/mL) compared with normal (286.10 ± 70.04 ng/mL, P < 0.01) and Her-2 positive cases (217.75 ± 60.59 ng/mL, P < 0.0001). In Her-2 negative cases, the HB-EGF concentrations (179.16 ± 118.81 pg/mL) were highly significant compared with normal (14.92 ± 17.33 pg/mL, P < 0.001). IL-6 concentrations were increased significantly in both the breast cancer phenotypes as compared with normal ( P < 0.001). Conclusion The specific expression pattern of annexinA2 and HB-EGF in triple-negative breast cancer tissues, increased secretion compared with normal cells, and their major role in the regulation of EGFR downstream signalling makes these molecules as a potential tissue and serum biomarker and an excellent therapeutic target in Her-2 negative breast cancer.

Rehabilitation of orbital defect with silicone orbital prosthesis retained by dental implants.

Orbital defects can result from cancer, birth anomalies, or trauma leading to an onslaught of problems in the function and psyche of the patient. These defects are restored by surgical reconstruction and followed by placement of orbital prosthesis for cosmetic makeup. The use of dental implants in retaining orbital prosthesis improves patient acceptance of the prosthesis owing to better retention and stability than conventional adhesive retained prosthesis. This case report describes a custom-made magnetic retentive assembly anchored by a dental implant which offers the orbital prosthesis the simplicity of self-alignment and ease of use.

Genomic DNA of MCF-7 breast cancer cells not an ideal choice as positive control for PCR amplification based detection of Mouse Mammary Tumor Virus-Like Sequences.

The identification of the etiology of breast cancer is a crucial research issue for the development of an effective preventive and treatment strategies. Researchers are exploring the possible involvement of Mouse Mammary Tumor Virus (MMTV) in causing human breast cancer. Hence, it becomes very important to use a consistent positive control agent in PCR amplification based detection of MMTV-Like Sequence (MMTV-LS) in human breast cancer for accurate and reproducible results. This study was done to investigate the feasibility of using genomic DNA of MCF-7 breast cancer cells to detect MMTV-LS using PCR amplification based detection. MMTV env and SAG gene located at the 3' long terminal repeat (LTR) sequences were targeted for the PCR based detection. No amplification was observed in case of the genomic DNA of MCF-7 breast cancer cells. However, the 2.7 kb DNA fragment comprising MMTV env and SAG LTR sequences yielded the products of desired size. From these results it can be concluded that Genomic DNA of MCF-7 cell is not a suitable choice as positive control for PCR or RT-PCR based detection of MMTV-LS. It is also suggested that plasmids containing the cloned genes or sequences of MMTV be used as positive control for detection of MMTV-LS.

Obstructive Jaundice Secondary to Primary Duodenal Lymphoma with CMV Duodenitis Causing Upper GI Bleed in Retro-Positive Patient: A Case Report.

Gastrointestinal (GI) tract is the most common site of extranodal lymphoma. Primary GI lymphoma constitutes a small amount of all lymphomas. Primary duodenal lymphoma presenting initially with obstructive jaundice is very rare. Primary B-cell lymphoma of the duodenum was shown to be the cause of biliary obstruction in a retropositive male, which was proved by endoscopic biopsy. Histopathology also showed cytomegalovirus inclusion bodies with duodenitis.

Anesthetic management of a patient with bicuspid aortic valve and Hashimoto's thyroiditis posted for abdominal hysterectomy.

Bicuspid aortic valve is the most common birth defect affecting the heart and is present in 1-2% of the population. The abnormal valve structure leads to turbulent flow, fibrosis, calcification, and aortic stenosis. Aortic stenosis increases perioperative morbidity and mortality. Anesthetic techniques that reduce systemic vascular resistance (regional neuraxial techniques) must be used with extreme caution. Hashimoto's disease or chronic thyroiditis or autoimmune thyroiditis is the most common cause of hypothyroidism in adults. Regional anesthesia is preferred in patients with hypothyroidism as recovery from general anesthesia may be delayed by hypothermia, respiratory depression, or slow drug biotransformation. This is a case report of anesthetic management of a middle-aged female with co-existing aortic stenosis, hypothyroidism, and fibroid uterus posted for abdominal hysterectomy.

Spectroscopic, magnetic and thermal studies of Co(II), Ni(II), Cu(II) and Zn(II) complexes of 3-acetylcoumarin-isonicotinoylhydrazone and their antimicrobial and anti-tubercular activity evaluation.

Co(II), Ni(II), Cu(II) and Zn(II) complexes with a new heterocyclic Schiff base derived by the condensation of isonicotinoylhydrazide and 3-acetylcoumarin have been synthesized. ¹H, ¹³C and 2D HETCOR NMR analyses confirm the formation of title compound and existence of the same in two isomeric forms. The metal complexes were characterized on the basis of various spectroscopic techniques like electronic, EPR, IR, ¹H and ¹³C NMR studies, elemental analysis, magnetic properties and thermogravimetric analysis, and also by the aid of molar conductivity measurements. It is found that the Schiff base behaves as a monobasic tridentate ligand coordinating in the imidol form with 1:1 metal to ligand stoichiometry. Trigonal bipyramidal geometry has been assigned for Ni(II) and Cu(II) complexes, while tetrahedral for Co(II) and Zn(II) complexes. The compounds were subjected to antimicrobial and anti-tubercular activity screening using serial broth dilution method and Minimum Inhibitory Concentration (MIC) is determined. Zn(II) complex has shown significant antifungal activity with an MIC of 6.25 µg/mL while Cu(II) complex is noticeable for antibacterial activity at the same concentration. Anti-TB activity of the ligand has enhanced on complexation with Co(II) and Ni(II) ions.

A study of anti-inflammatory and analgesic activity of new 2,3-disubstituted 1,2-dihydroquinazolin-4(3h)-one derivative and its transition metal complexes.

A new 2,3-disubstituted 1,2-dihydroquinazolin-4(3H)-one derivative namely 2-hydroxy-2-ethyl-(3-carboxylideneamino)-3-(2-(4-methyl-phenyl))-1,2-dihydroquinazolin-4(3H)-one (HECMDQ) is synthesized employing a modified method in higher yield and is complexed with Co(II), Ni(II), Cu(II) and Zn(II) metal ions in order to study its coordinating behavior. All the complexes were characterized by various physicochemical (analytical, IR, NMR, Electron Paramagnetic Resonance (EPR), mass, Thermogravimetric Analysis Differential Thermogravimetric Analysis (TGA-DTA)) methods. The molar conductivity measurements in N,N-dimethylformamide (DMF) solution indicate the non-electrolytic nature of complexes. IR spectral analysis reveal that coordination takes place through the deprotonated hydroxyl group, azomethine nitrogen and carbonyl oxygen. Four coordinated geometry was assigned to all the complexes on the basis of spectral studies. The anti-inflammatory activities of compounds are moderate. Co(II) complex exhibited highest activity among all the complexes. At lower dose level activity of Ni(II) and Cu(II) complexes is more compared to that of ligand. The analgesic activity of ligand has enhanced on complexation with Co(II), Ni(II) and Zn(II) metal ions. Among the compounds studied Co(II) complex has shown highest activity and is comparable with standard used.

Transition metal complexes of 3-aryl-2-substituted 1,2-dihydroquinazolin-4(3H)-one derivatives: new class of analgesic and anti-inflammatory agents.

Five-coordinate, neutral transition metal complexes of newly designed pyridine-2-ethyl-(3-carboxylideneamino)-3-(2-phenyl)-1,2-dihydroquinazolin-4(3H)-one (L) were synthesized and characterized. The structure of ligand is confirmed by single crystal X-ray diffraction studies. The compounds were evaluated for the anti-inflammatory activity by carrageenan-induced rat paw edema model while their analgesic activity was determined by acetic acid-induced writhing test in mice wherein the transition metal complexes were found to be more active than the free ligand.