Assessing the cooling/lubricating agencies for sustainable alternatives during machining of Nimonic 80: Economic and environmental impacts.

Developing sustainable manufacturing methods that balance environmental and economic aspects is challenging. A comprehensive analysis of the economics of machining and carbon emissions is essential to encourage adopting sustainable practices. This work presents the machinability and comparative sustainability analysis of Nimonic 80 superalloy when it is machined utilizing a novel, environmentally friendly vegetable oil-based hybrid nanofluid-minimum quantity lubrication (MQL) and liquid carbon dioxide (LCO2) technique. The main objective is to comprehend the efficacy of the proposed approach on tool life, surface roughness, power consumption, total machining costs, and carbon emissions. Compared to other machining conditions, the use of hybrid nanofluid-MQL under 100 m/min cutting speed prevented rapid flank wear and considerably increased tool life by about 17-59 %. The change in cutting speed from 100 to 150 m/min has resulted in reduced tool life about 13-42 % under the selected environments. In addition, when compared to dry, flood, and MQL machining, the use of hybrid nanofluid-MQL and LCO2 reduced surface roughness by around 16-45 % at 150 m/min. Sustainability analysis revealed that machining at 150 m/min resulted in decreased costs ranging from 6.1 % to 36.4 % for selected cutting environments. Applying hybrid nanofluid-MQL lowered carbon emissions by 16.83 %, whereas LCO2 reduced carbon emissions by 14.6 % at 100 m/min. At 150 m/min, hybrid nanofluid-MQL and LCO2 lowered carbon emission by 22.3 % and 21.5 % at 150 m/min compared to dry machining. Compared to alternative cutting environments, hybrid nanofluid-MQL and LCO2 applications have longer tool lives, lower machining costs, and carbon emissions. As a result, they are economical and environmentally friendly.

'PartBreCon' study. A UK multicentre retrospective cohort study to assess outcomes following PARTial BREast reCONstruction with chest wall perforator flaps.

BACKGROUND: Partial breast reconstruction with a pedicled chest wall perforator flap (CWPF) enables breast conservation in a higher tumour: breast volume ratio scenario. Since there is limited evidence, this retrospective cohort study aimed to ascertain immediate (30-days) and medium-term (follow-up duration) surgical outcomes. METHODS: STROBE-compliant protocol ascertained CWPF outcomes between March 2011-March 2021. UK centres known to perform CWPF were invited to participate if they performed at least 10 cases. Data were retrospectively collected, including patient demographics, tumour and treatment characteristics, and surgical and oncological outcomes. Statistical analysis (R™) included multivariable logistic regression and sensitivity analysis. RESULTS: Across 15 centres, 507 patients with median age (54 years, IQR; 48-62), body mass index (25.4 kg/m2, IQR; 22.5-29), tumour size (26 mm, IQR; 18-35), and specimen weight (62 g, IQR; 40-92) had following flap types: LiCAP (54.1%, n = 273), MiCAP/AiCAP (19.6%, n = 99), LiCAP + LTAP (19.8%, n = 100) and TDAP (2.2%, n = 11). 30-days complication rates were in 12%: haematoma (4.3%, n = 22), wound infection (4.3%, n = 22), delayed wound healing (2.8%, n = 14) and flap loss (0.6%, n = 3; 1 full) leading to readmissions (2.6%, n = 13) and re-operations (2.6%, n = 13). Positive margins (n = 88, 17.7%) led to 15.9% (n = 79) re-excisions, including 7.5% (n = 37) at the planned 2nd of 2-stage surgery and 1.8% (n = 9) mastectomy. At median 23 months (IQR; 11-39) follow-up, there were 1.2% (n = 6) symmetrisations; recurrences: local (1%), regional/nodal (0.6%) and distant (3.2%). CONCLUSIONS: This large multicentre cohort study demonstrates acceptable complication and margin re-excision rates. CWPF extends the range of breast conservation techniques. Further studies are required for long-term oncological outcomes.

Treatment of periocular lentigo maligna with topical 5% Imiquimod: a review.

Lentigo Maligna is a benign subtype of melanoma in situ and can progress to lentigo maligna melanoma, which is invasive. Complete surgical excision is the gold standard of treatment but requires large margins. If affecting the peri-ocular region, surgical excision leads to extensive defects, complex reconstructions, and functional impairment of the protection of the ocular surface. Here we review the reported literature about the use of Imiquimod 5% topical cream for lentigo maligna of the eyelid, the treatment outcomes, side effects and tolerance. In addition, the side effects of imiquimod treatment of non-LM lesions are described to help better inform the decision-making process. Treatment for peri-ocular Lentigo maligna showed a 56-86% complete treatment response and a 90% tolerability rate. However, reported treatment protocols vary and histopathological confirmation of clearance was only obtained in 56%. Further studies are required to determine the optimal treatment protocol to maximise clearance rates. Overall, Imiquimod was well tolerated in the peri-ocular area.

Glycemic, insulinemic and methylglyoxal postprandial responses to starches alone or in whole diets in dogs versus cats: Relating the concept of glycemic index to metabolic responses and gene expression.

Species differences between domestic cats (Felis catus) and dogs (Canis familiaris) has led to differences in their ability to digest, absorb and metabolize carbohydrates through poorly characterized mechanisms. The current study aimed to first examine biopsied small intestine, pancreas, liver and skeletal muscle from laboratory beagles and domestic cats for mRNA expression of key enzymes involved in starch digestion (amylase), glucose transport (sodium-dependent SGLTs and -independent glucose transporters, GLUT) and glucose metabolism (hexokinase and glucokinase). Cats had lower mRNA expression of most genes examined in almost all tissues compared to dogs (p < 0.05). Next, postprandial glucose, insulin, methylglyoxal (a toxic glucose metabolite) and d-lactate (metabolite of methylglyoxal) after single feedings of different starch sources were tested in fasted dogs and cats. After feeding pure glucose, peak postprandial blood glucose and methylglyoxal were surprisingly similar between dogs and cats, except cats had a longer time to peak and a greater area under the curve consistent with lower glycolytic enzyme expression. After feeding starches or whole diets to dogs, postprandial glycemic response, glycemic index, insulin, methylglyoxal and d-lactate followed reported glycemic index trends in humans. In contrast, cats showed very low to negligible postprandial glycemic responses and low insulin after feeding different starch sources, but not whole diets, with no relationship to methylglyoxal or d-lactate. Thus, the concept of glycemic index appears valid in dogs, but not cats. Differences in amylase, glucose transporters, and glycolytic enzymes are consistent with species differences in starch and glucose handling between cats and dogs.

A prospective, single-arm, multicentre clinical evaluation of a new localisation technique using non-radioactive Magseeds for surgery of clinically occult breast lesions.

AIM: To evaluate the safety, usefulness, and outcome of Magseed localisation for surgery of non-palpable breast lesions in a non-experimental setting. MATERIALS AND METHODS: An audit was undertaken of a prospectively maintained database of patients who had undergone breast surgery under Magseed guidance in two high-volume institutions in the UK. Patients were selected for Magseed localisation depending on service convenience. Wire localisations were used in other patients in accordance with previous normal practice. One hundred and thirty-nine Magseed localisaton procedures were performed between September 2017 and March 2019. Data were collected on age, body mass index, size, bra cup size, weight of specimen, surgery, histology, re-excision rate, and time and mode of insertion of seeds. RESULTS: A total of 137 patients had Magseed localisation with a total of 139 seeds. Sixteen patients had a diagnostic procedure and 121 had therapeutic surgery. The distribution of procedures were similar between the two institutes (n=63 and n=74). Mean age was 60 (range 28-81) years. The majority of seeds were placed under ultrasound guidance (n=112) and 25 lesions were targeted under stereo guidance. Mean size of the lesions was 15.2 (range 1-85) mm. The mean weight of the specimen was 75.5 (range 2-1,900) g. The mean body mass index was 30.56 (range 18.1-48.3). All Magseeds and index lesions were retrieved. The re-excision rate for patients who underwent therapeutic surgery was 14.8% (n=18). CONCLUSION: The Magseed localisation technique of non-palpable breast lesions is a safe, easy procedure, and comes with the advantage of better utilisation of theatre and radiology resources. The re-excision rate in this series is lower than the national average.

PVA/SA/TiO2-CUR patch for enhanced wound healing application: In vitro and in vivo analysis.

Wound healing is a complex multistep process. Wound healing materials should have good antibacterial activity against wound infection causing microbes. Curcumin has effective antimicrobial activity, anti-inflammatory and antioxidant property. Titanium dioxide (TiO2) is a biocompatible, nontoxic material used for many biomedical applications. The Usage of curcumin tagged TiO2 nanoparticles for wound healing activity is promising due to the properties of both curcumin and TiO2. We have synthesized curcumin tagged TiO2 nanoparticles. The synthesized materials are characterized with XRD, FTIR and TEM. TiO2-Cur nanocomposite was incorporated into poly vinyl alcohol (PVA) and sodium alginate (SA) patch. The PVA/SA/TiO2-Cur patch was prepared by gel casting method. Antibacterial efficiency of PVA/SA/TiO2-Cur patch was analyzed. Further, in vivo studies conducted on Wister rats confirmed the enhanced wound healing property of the PVA/SA/TiO2-Cur patch. Our results suggest that this could be an ideal biomaterial for wound dressing applications.

Zinc Oxide nanoparticles induce oxidative and proteotoxic stress in ovarian cancer cells and trigger apoptosis Independent of p53-mutation status.

Ovarian cancer continues to be the most lethal among gynecological malignancies and the major cause for cancer-associated mortality among women. Limitations of current ovarian cancer therapeutics is highlighted by the high frequency of drug-resistant recurrent tumors and the extremely poor 5-year survival rates. Zinc oxide nanoparticles (ZnO-NPs) have shown promise in various biomedical applications including utility as anti-cancer agents. Here, we describe the synthesis and characterization of physical properties of ZnO-NPs of increasing particle size (15 nm - 55 nm) and evaluate their benefits as an ovarian cancer therapeutic using established human ovarian cancer cell lines. Our results demonstrate that the ZnO-NPs induce acute oxidative and proteotoxic stress in ovarian cancer cells leading to their death via apoptosis. The cytotoxic effect of the ZnO-NPs was found to increase slightly with a decrease in nanoparticle size. While ZnO-NPs caused depletion of both wild-type and gain-of-function (GOF) mutant p53 protein in ovarian cancer cells, their ability to induce apoptosis was found to be independent of the p53-mutation status in these cells. Taken together, these results highlight the potential of ZnO-NPs to serve as an anti-cancer therapeutic agent for treating ovarian cancers independent of the p53 mutants of the cancer cells.

Axillary tumour burden in women with one abnormal node on ultrasound compared to women with multiple abnormal nodes.

AIM: To determine if the number of abnormal nodes seen on preoperative axillary ultrasound (AUS) is a predictor of the number of positive nodes at histology for women with needle-biopsy-proven positive nodes. MATERIALS AND METHODS: This prospective multicentre cohort study included consecutive patients with early breast cancer who had needle-biopsy-proven positive nodes on AUS and underwent axillary lymph node dissection (ALND) between October 2015 and July 2016. The number of abnormal nodes at preoperative AUS was recorded by breast radiologists or radiographers. RESULTS: One hundred and twenty-three patients were included in the study. The median age of the women was 62 (range 30-93) years. Fifty-four of the 123 (44%) women had one abnormal node, whereas 69 (56%) had multiple abnormal nodes on AUS. Forty of the 123 (33%) women had two or fewer nodes with metastases at histology after ALND. Tumours ≤20 mm (p<0.001) and one abnormal node on AUS (p<0.001) were associated with two or fewer nodes with metastases at ALND. Both remained significant in logistic regression analysis. The likelihood of at least three metastases based on the combination of these two factors had 95% sensitivity (79 of 83), 35% specificity (14 of 40), a negative predictive value of 78% (14 of 18), and a positive predictive value of 75% (79 of 105). CONCLUSION: Among women with needle-biopsy-proven positive nodes, around three in four women (78%) with an invasive tumour ≤2 cm and one abnormal node on AUS have two or fewer positive nodes at ALND. These women are overtreated by upfront ALND and can be offered sentinel node biopsy (SNB).

MARGINAL MICROLEAKAGE PROPERTIES OF ACTIVA BIOACTIVE RESTORATIVE AND NANOHYBRID COMPOSITE RESIN USING TWO DIFFERENT ADHESIVES IN NON CARIOUS CERVICAL LESIONS - AN IN VITRO STUDY.

BACKGROUND: In clinical practice, the restoration of non-carious cervical lesions is a challenge, because most of the time the cervical margin is located in cementum or dentin. This characteristic makes the cervical margin more susceptible to microleakage, causing cavosurface stains, postoperative sensitivity and also favours the incidence of carious lesions. AIM: To compare and evaluate the microleakage in class V lesions restored with Activa Bioactive restorative and nanohybrid composite resin using two different bonding agents. METHODOLOGY: In this study, 50 class V cavities were prepared in freshly extracted teeth. The samples were randomly divided into 5 groups (n=10), depending on the type of restorative material and bonding agent: Group 1 - Activa Bioactive (Pulpdent, USA) + No bonding, Group 2 - Activa Bioactive + Tetric N Bond (Ivoclar Vivadent, Colombia),Group 3 - Activa Bioactive + G Bond (GC Corp., Tokyo, Japan), Group 4 - Nanohybrid Composite (Ivoclar Vivadent, Colombia) + Tetric N Bond, Group 5 - Nanohybrid Composite + G Bond. The samples were restored with their respective material based on the group. After curing all the specimens were subjected to thermocycling and cyclic loading. Specimens were stained with 2% rhodamin b dye and evaluated for dye penetration. RESULTS: Results were obtained based on Kruskal Wallis and Mann Whitney U- test. CONCLUSION: Within the limitations of this study, none of the materials were free from microleakage. All the materials showed more microleakage at gingival margins compared to occlusal margins. Among all the groups Activa Bioactive restorative when used in combination with Tetric N Bond showed the least microleakage.

MINIMAL INVASIVE SURGICAL APPROACH IN THEMANAGEMENT OF COMMINUTED CROWN-ROOT FRACTURE- A CASE REPORT.

Comminuted root fractures have a questionable prognosis and present with limited treatment options. In the following case, a comminuted crown root fracture in relation to maxillary left central incisor was managed with a minimally invasive surgical approach. The procedure involved repairing the multiple fracture lines in the root with Biodentine following the endodontic therapy and root resection. The patient was found to be asymptomatic at the end of a follow up period of ten months.

Pharmacological evaluation of novel alagebrium analogs as methylglyoxal scavengers in vitro in cardiac myocytes and in vivo in SD rats.

BACKGROUND: Methylglyoxal (MG) is a byproduct of glucose metabolism and an inducer of advanced glycation end products (AGEs). AGEs are implicated in the pathogenesis of diabetes as well as hypertension. Most of the currently available MG scavengers are non-specific and have other effects as well. Alagebrium (ALA), developed by Alteon Corporation is a MG scavenger. Thus the aim of the present study was to investigate the potential of novel ALA analogs as possible MG scavengers and whether they could prevent any deleterious effects of MG. METHODS AND RESULTS: MG levels were measured by HPLC. The different biochemical and molecular parameters were measured by assay kits, RT-PCR and immunocytochemistry. Out of the 15 ALA analogs tested in vitro, compound no. 13 was found to be an effective inhibitor of MG in a concentration and time dependent manner. Compound no. 13 significantly attenuated the MG levels in vitro in MG treated cultured H9C2 cardiomyocytes as well as in vivo in MG treated SD rats. MG induced oxidative stress and apoptosis were attenuated by pretreatment of H9C2 cardiac myocytes with compound no. 13. MG induced cardiac hypertrophy and apoptosis were also attenuated by treating MG treated SD rats with compound no. 13. CONCLUSION: Our results indicate compound 13 as an effective inhibitor of MG in vitro in cultured cardiomyocytes and in vivo in SD rats and thus it may prove very useful in blocking the multiple deleterious effects of MG, including AGEs and vascular complications of diabetes.

Alagebrium attenuates methylglyoxal induced oxidative stress and AGE formation in H9C2 cardiac myocytes.

AIM: Diabetes mellitus associated cardiovascular complications are a leading cause of morbidity and mortality worldwide. Methylglyoxal (MG) is a reactive ketoaldehyde and a byproduct of glucose metabolism and an inducer of advanced glycation endproducts (AGEs). Alagebrium (ALA) is an AGEs crosslink breaker, however, the effects of ALA on MG levels and its consequences in cultured rat cardiomyocytes are not known. The aim of the present study was to examine the effect of high glucose and MG on cultured rat cardiomyocytes and to investigate whether ALA could prevent any deleterious effects of high glucose and MG in these cells. MAIN METHODS: MG levels were determined by HPLC. The expression of different genes was measured by RT-PCR. Oxidative stress and AGEs formation was determined by DCF probe and immunocytochemistry respectively. KEY FINDINGS: High glucose- and MG treated- cardiomyocytes developed a significant increase in MG, and the expression for caspase-3, Bax, RAGE and NF-KB, which were all attenuated after pretreatment with ALA. A significant increase in reactive oxygen species generation and AGEs formation in high glucose- and MG treated- cultured cardiomyocytes was also observed, which was attenuated after pretreatment with ALA. SIGNIFICANCE: ALA may have a preventive role against the deleterious effects of high glucose and MG in the heart. Prevention of dicarbonyl-induced AGEs, by safer and specific scavengers of MG is an attractive therapeutic option.

Control of Aedes aegypti and Ae. albopictus, the vectors of dengue and chikungunya, by using pheromone C21 with an insect growth regulator: Results of multicentric trials from 2007-12 in India.

BACKGROUND & OBJECTIVES: Aedes mosquito control has gained much importance nowadays in view of rise in number of reported cases of dengue and chikungunya in India and other countries. In the present study, C21 attracticide (containing a pheromone and an insect growth regulator­IGR, developed by Defence Research and Development Establishment (DRDE), Gwalior, India was tested for its feasibility for surveillance and control of Aedes mosquito in a multicentric mode from October 2007 to June 2012 in urban (Delhi, and Bengaluru district, Karnataka) and suburban (Alappuzha district, Kerala) settings of the country in three phases. METHODS: Across the randomly selected households in each study area, two to four containers treated with attracticide (experimental) and untreated (control) were placed and monitored by trained surveillance workers on weekly/ fortnightly basis for determining the presence of eggs, larvae and pupae. Container positivity, percent larvae, egg and pupae collected were determined during different phases and analyzed statistically using SPSS 18.0. RESULTS: Container positivity was found statistically significant at Bengaluru and Alappuzha, Kerala while in Delhi, it was found non-significant. Eggs collected from experimental containers were significantly higher in comparison to control at all the locations except Delhi. Also larvae collected from control containers were significantly higher at all the locations except Bengaluru. Pupae collected from control containers remained significantly higher at all the locations as no pupal formation was recorded from experimental containers. INTERPRETATION & CONCLUSION: The use of C21 attracticide hampered pupal formation, thus inhibiting adult population in the study areas. The study established that C21 attracticide was efficacious in the field conditions and has potential for use in surveillance and management of dengue and chikungunya mosquitoes.

Competitive immunochromatographic assay for the detection of thiodiglycol sulfoxide, a degradation product of sulfur mustard.

An immunochromatographic assay (ICA) based on the competitive antigen-coated format using colloidal gold as the label was developed for the detection of thiodiglycol sulfoxide (TDGO), an important metabolite and degradation compound of sulphur mustard (SM). The ICA test strip consisted of a membrane with a detection zone, a sample pad and an absorbent pad. The membrane was separately coated with hapten-OVA conjugate (test line) and anti-rabbit mouse IgG (control line). The visual detection limit for TDGO by ICA detection was found to be 10 µg mL(-1). For validation, the ICA results obtained for spiked water samples were in good agreement with those obtained by indirect competitive inhibition enzyme-linked immunosorbent assay (ELISA) for TDGO. The assay time for detection was less than 10 min. The developed ICA has the potential to be a useful on-site screening tool for the retrospective detection of SM in environmental samples.

What makes a feline fatal in Toxoplasma gondii's fatal feline attraction? Infected rats choose wild cats.

Toxoplasma gondii is an indirectly transmitted protozoan parasite, of which members of the cat family (Felidae) are the only definitive hosts and small mammals such as rats serve as intermediate hosts. The innate aversion of rodents to cat odor provides an obstacle for the parasite against successful predation by the feline definitive host. Previous research has demonstrated that T. gondii appears to alter a rat's perception of the risk of being preyed upon by cats. Although uninfected rats display normal aversion to cat odor, infected rats show no avoidance and in some cases even show attraction to cat odor, which we originally termed the "Fatal Feline Attraction." In this study, we tested for the first time whether the "Fatal Feline Attraction" of T. gondii-infected rats differed according to the type of feline odor used, specifically whether it came from domestic cats (Felis silvestris catus) or wild cats-cheetahs (Acinonyx jubatus) or pumas (Felis concolor). In two-choice odor trials, where wild and domestic cat odors were competed against one another, consistent with previous findings we demonstrated that infected rats spent more time in feline odor zones compared with uninfected rats. However, we further demonstrated that all cat odors are not equal: infected rats had a stronger preference for wild cat odor over that of domestic cats, an effect that did not differ significantly according to the type of wild cat odor used (cheetah or puma). We discuss these results in terms of the potential mechanism of action and their implications for the current and evolutionary role of wild, in addition to domestic, cats in transmission of T. gondii.

Synthesis of some novel phosphorylated and thiophosphorylated benzimidazoles and benzothiazoles and their evaluation for larvicidal potential to Aedes albopictus and Culex quinquefasciatus.

Series of benzimidazole and benzothiazole linked phosphoramidates and phosphoramidothioates (5a-j) and benzimidazole linked phenylphosphoramidates and phenylphosphoramidothioates (10a-e) were synthesized. The title compounds were preliminary screened for mosquito larvicidal properties against Aedes albopictus and Culex quinquefasciatus at different concentration from 40 to 5 mg/L. Among the screened compounds three compounds revealed potential larvicidal effects with 100% mortality in the order of 10e>5j>5e. Compound 10e was found to be the most toxic compound to Ae. albopictus and Cx. quinquefasciatus. The LC50 of 10e against Ae. albopictus was found to be 6.42 and 5.25 mg/L at 24 and 48 h, respectively, whereas it was 7.01 and 3.88 mg/L, respectively in Cx. quinquefasciatus. Temephos was used as positive control.

Methylglyoxal, a reactive glucose metabolite, increases renin angiotensin aldosterone and blood pressure in male Sprague-Dawley rats.

BACKGROUND: The majority of people with diabetes develop hypertension along with increased activity of the renin-angiotensin system. Methylglyoxal, a reactive glucose metabolite, is elevated in diabetic patients. We investigated the effects of methylglyoxal on the renin-angiotensin system and blood pressure. METHODS: Male Sprague-Dawley rats were treated with a continuous infusion of methylglyoxal with a minipump for 4 weeks. Organs/tissues and cultured vascular smooth muscle cells (VSMCs) were used for molecular studies. High-performance liquid chromatography, Western blotting, and quantitative real-time polymerase chain reaction were used to measure methylglyoxal, proteins, and mRNA, respectively. Small interfering RNA for angiotensinogen and the receptor for advanced glycation endproducts (RAGE) were used to study mechanisms. RESULTS: Methylglyoxal-treated rats developed a significant increase in blood pressure and plasma levels of aldosterone, renin, angiotensin, and catecholamines. Methylglyoxal level and protein and mRNA for angiotensin, AT1 receptor, adrenergic α1D receptor, and renin were significantly increased in the aorta and/or kidney of methylglyoxal-treated rats, a novel finding. Alagebrium attenuated the above effects of methylgloyxal. Treatment of cultured VSMCs with methylglyoxal or high glucose (25 mM) significantly increased cellular methylglyoxal and protein and mRNA for nuclear factor kappa B (NF-κB), angiotensin, AT1 receptor, and α1D receptor, which were prevented by inhibition of NF-κB, and by alagebrium. Silencing of mRNA for RAGE prevented the increase in NF-kB induced by methylglyoxal. Silencing of mRNA for angiotensinogen prevented the increase in NF-κB, angiotensin, AT1 receptor, and α1D receptor. CONCLUSIONS: Methylglyoxal activates NF-κB through RAGE and thereby increases renin-angiotensin levels, a novel finding, and a probable mechanism of increase in blood pressure.

Interactions between xylene-linked carbamoyl bis-pyridinium mono-oximes and organophosphates inhibited-AChE: a kinetic study.

Reactivation of organophosphate (OP) inhibited acetylcholinesterase (AChE) by oximes is inadequate against various OP nerve agents known till date owing to their diverse structural features. As a consequence, in the past decades widespread research programs have been undertaken independently throughout the world to develop and identify more effective oxime reactivators. The efficacy of oxime reactivators is estimated through different in vitro and in vivo models using AChE from various sources against structurally different OPs. In the present study, reactivation kinetics of OP (paraoxon, DFP, sarin and VX) inhibited AChE by xylene linked carbamoyl bis-pyridinum mono-oximes have been described. It was found that the reactivation potency of tested oximes varied with the inhibitors used as 5l (4-carbamoyl-2' hydroxyiminomethyl-1-1'-(1,3-phenylenedimethyl)-bis-pyridinium dibromide) was found to be the most effective reactivator against paraoxon. In case of DFP, 5k (3-carbamoyl-2' hydroxyiminomethyl-1-1'-(1,3-phenylenedimethyl)-bis-pyridinium dibromide) showed best reactivation while in case of sarin 5e (3-carbamoyl-2' hydroxyiminomethyl-1-1'-(1,4-phenylenedimethyl)-bis-pyridinium dibromide) exhibited outstanding reactivation ability in comparison to standard oximes (2-PAM, obidoxime and TMB-4) as indicated by its highest value of second order reactivation rate constant (k(r2)) 3.26 mM⁻¹ min⁻¹. The enhanced reactivation efficacy of oximes may be attributed to the optimal length of xylene linker which facilitates appropriate positioning of carbamoyl function to the peripheral anionic site (PAS) and extending the oxime moiety to the active site of AChE.

Increased methylglyoxal formation with upregulation of renin angiotensin system in fructose fed Sprague Dawley rats.

The current epidemic of obesity and type 2 diabetes is attributed to a high carbohydrate diet, containing mainly high fructose corn syrup and sucrose. More than two thirds of diabetic patients have hypertension. Methylglyoxal is a highly reactive dicarbonyl generated during glucose and fructose metabolism, and a major precursor of advanced glycation end products (AGEs). Plasma methylglyoxal levels are increased in hypertensive rats and diabetic patients. Our aim was to examine the levels of methylglyoxal, mediators of the renin angiotensin system and blood pressure in male Sprague-Dawley rats treated with a high fructose diet (60% of total calories) for 4 months. The thoracic aorta and kidney were used for molecular studies, along with cultured vascular smooth muscle cells (VSMCs). HPLC, Western blotting and Q-PCR were used to measure methylglyoxal and reduced glutathione (GSH), proteins and mRNA, respectively. Fructose treated rats developed a significant increase in blood pressure. Methylglyoxal level and protein and mRNA for angiotensin II, AT1 receptor, adrenergic α1D receptor and renin were significantly increased, whereas GSH levels were decreased, in the aorta and/or kidney of fructose fed rats. The protein expression of the receptor for AGEs (RAGE) and NF-κB were also significantly increased in the aorta of fructose fed rats. MG treated VSMCs showed increased protein for angiotensin II, AT1 receptor, and α1D receptor. The effects of methylglyoxal were attenuated by metformin, a methylglyoxal scavenger and AGEs inhibitor. In conclusion, we report a strong association between elevated levels of methylglyoxal, RAGE, NF-κB, mediators of the renin angiotensin system and blood pressure in high fructose diet fed rats.

Large primary intraorbital hydatid cyst in elderly.

We report a case of solitary, primary intraorbital hydatid cyst in a elderly female aged 80 years who presented with nontender, nonpulsatile proptosis of left eye with diminution of vision. MRI scan of the head and the orbits, revealed a retro-bulbar cyst. Surgical excision was performed by employing a lateral orbitotomy approach. Histopathology report confirmed hydatid cyst.