How to Avoid the Detachment of Threads of Varnish during Production,through Cutting and Drawing,in the Manufacture of Lids with a ‘Twist-Off’ Mechanism Used for the Closure of Glass Containers

The lids of glass containers which have a ‘twist-off’ mechanism are manufactured from tinplate through a process of cutting and drawing. Previously, the tinplate was protected with a double layer of a certain epoxy-phenolic varnish. During cutting, the detachment of threads of varnish is produced, and these may reach more than 150 microns in diameter. These threads stick to the equipment, thus hindering the shaping process. After manufacturing thousands of lids, stops must inevitably be made in production in order to clean machinery. Through the application of a fractioned design of experiment (DoE) application, carried out on an industrial scale, the effect of a number of factors on the detachment of threads of varnish was studied. Some to these factors refer to coating, others to the substratum and others to the process of cutting and drawing. It is concluded that the detachment is greater in the disk areas which are parallel to the forward direction of the production line. This problem could be substantially reduced, and even eliminated, if the direction of the rolling of the sheet metal were perpendicular to that of the forward direction of the production line, if the blank-holder is situated at 4 bar, if the time between the curing process and cutting is no more than 3threedays, if the clearance in the cutting is situated at 0.06 mm, and if the grammage of the varnish and the grammage of the layer of tin are increased.     

Genetic profile of adenoid cystic carcinomas (ACC) with high-grade transformation versus solid type

Background

ACC can occasionally undergo dedifferentiation also referred to as high-grade transformation (ACC-HGT). However, ACC-HGT can also undergo transformation to adenocarcinomas which are not poorly differentiated. ACC-HGT is generally considered to be an aggressive variant of ACC, even more than solid ACC. This study was aimed to describe the genetic changes of ACC-HGT in relation to clinico-pathological features, and to compare results to solid ACC.

Methods

Genome wide DNA copy number changes were analyzed by microarray CGH in ACC-HGT, four with transformation into moderately differentiated adenocarcinoma (MDA) and two into poorly differentiated carcinoma (PDC), and five solid ACC. In addition, Ki67 index and p53 immunopositivity was assessed.

Results

ACC-HGT carried fewer copy number changes compared to solid ACC. Two ACC-HGT cases harboured a breakpoint at 6q23, near the cMYB oncogene. The complexity of the genomic profile concurred with the clinical course of the patient. Among the ACC-HGT, p53 positivity significantly increased from the conventional to the transformed (both MDA and PDC) component.

Conclusion

ACC-HGT may not necessarily reflect a more advanced stage of tumor progression, but rather a transformation to another histological form in which the poorly differentiated forms (PDC) presents a genetic complexity similar to the solid ACC.     

Avaliação e manejo perioperatório de pacientes com diabetes melito. Um desafio para o anestesiologista

Diabetes mellitus (DM) is characterized by alteration in carbohydrate metabolism, leading to hyperglycemia and increased perioperative morbidity and mortality. It evolves with diverse and progressive physiological changes, and the anesthetic management requires attention regarding this disease interference in multiple organ systems and their respective complications. Patient's history, physical examination, and complementary exams are important in the preoperative management, particularly glycosylated hemoglobin (HbA1c), which has a strong predictive value for complications associated with diabetes. The goal of surgical planning is to reduce the fasting time and maintain the patient's routine. Patients with Type 1 DM must receive insulin (even during the preoperative fast) to meet the basal physiological demands and avoid ketoacidosis. Whereas patients with Type 2 DM treated with multiple injectable and/or oral drugs are susceptible to develop a hyperglycemic hyperosmolar state (HHS). Therefore, the management of hypoglycemic agents and different types of insulin is fundamental, as well as determining the surgical schedule and, consequently, the number of lost meals for dose adjustment and drug suspension. Current evidence suggests the safe target to maintain glycemic control in surgical patients, but does not conclude whether it should be obtained with either moderate or severe glycemic control.     

Preoperative vitamin C supplementation improves colorectal anastomotic healing and biochemical parameters in malnourished rats

Purposes

The objective of this study was to evaluate the effect of supplementation with vitamin C on intestinal anastomosis healing in malnourished rats.

Methods

Male Wistar rats were divided into three groups: (1) sham, well-nourished rats that received vehicle; (2) FR+Veh, rats that were subjected to food restriction and received vehicle; and (3) FR+VC, rats that were subjected to food restriction and received vitamin C. Four days before surgery, the animals received vitamin C (100 mg/kg/day) via gavage and underwent colon resection with anastomosis in a single plane. The survival rate of rats was monitored until day 7 after surgery. Regarding anastomosis tissues, we examined intra-abdominal adhesion index, hydroxyproline content, collagen density, inflammatory parameters, and oxidative damage to proteins and lipids.

Results

Malnutrition decreases body weight and increases mortality; the survival rate was 90 % in group 1, 60 % in group 2, and 80 % in group 3. Vitamin C was able to increase hydroxyproline concentration and density of collagen and decrease the intra-abdominal adhesion index, as well as the infiltration of neutrophils and oxidative damage to proteins in malnourished rats compared to group treated with vehicle.

Conclusions

Preoperative vitamin C supplementation can improve the intestinal anastomosis healing, biochemical alterations, and prolong survival in rats subjected to food restriction.

     

Expression and clinical significance of matrix metalloproteinase-2 and matrix metalloproteinase-9 in oral squamous cell carcinoma

To successfully establish a metastasis from an invasive carcinoma, the first step involves the degradation of the underlying basement membrane, which is mainly made up of type IV collagen. Matrix metalloproteinases (MMPs)-2 and -9 are thought to play an important role in its degradation because of their ability to destroy this type of collagen. In order to evaluate the prognostic significance of these proteases, we studied the expression of MMP-2 and -9 in series of 68 OSCC by immunohistochemistry. Of the oral carcinomas, 28% (n = 19) expressed MMP-2, and 17.6% (n = 12) expressed MMP-9. MMP-2 immunoreactivity was significantly higher in patients with alcohol consumption (p = 0.028) (OR = 4), and in those younger than 60 years (p = 0.041). MMP-9 immunostaining showed statistically significant association with the tumor grade of differentiation (p = 0.019), the T-stage (p = 0.05), and also with the alcohol intake (p = 0.04) (OR = 7.67). In the present study, although not statistically significant, we observed that immunoexpression of MMP-2 and MMP-9 was stronger in patients with lymph node metastasis (OR = 1.65 and 2.29, respectively). In patients without regional lymph node metastasis, positive MMP-9 immunostaining was related to poor survival rates (p = 0.02; OR = 5.8). MMP-2 and -9 are involved in the invasion process of oral cancer, and MMP-9 is related to poor prognosis in the subset of patients without neck node metastasis. Ethanol could enhance the carcinogenetic process in oral cavity through its influence in the expression of MMP-2 and -9.     

Immunoexpression and prognostic significance of TIMP-1 and -2 in oral squamous cell carcinoma

Matrix metalloproteinases (MMPs) are proteolytic enzymes that are capable of degrading different substrates within the extracellular matrix, and which are believed to be crucial for tumor invasion and metastasis. Tissue inhibitors of MMPs (TIMPs) can inhibit the action of MMPs but also can show a paradoxical poor prognostic effect. In order to evaluate the prognostic significance of TIMPs, we studied the expression of TIMP-1 and -2 in series of 68 oral squamous cell carcinomas (OSCC) by immunohistochemistry. Expression of TIMP-1 was detected in 45 cases (66.2%). In all of these TIMP-1 was expressed in tumoral tissue, and in 19 of them also in the surrounding stroma. In cancer tissue, TIMP-1 was observed in three patterns: homogeneous, central and irregular. Immunoreactivity for TIMP-2 was detected in 38 cases (56%) in tumoral tissue and 9 (13.2%) in the stroma. The expression pattern of TIMP-2 was the same three as TIMP-1 and one more: invasive front of tumoral nests. TIMP-1 expression was not correlated with clinical or pathological parameters. However, TIMP-2 was significantly correlated with T stage (p=0.03), TNM stage (p=0.01), local recurrence (p=0.04), and poor survival (p=0.03, odds ratio=2.75). TIMP-1 and TIMP-2 were significantly correlated with cyclin D1 (p=0.04; p=0.015, respectively) and p53 expressions (p=0.02; p=0.04, respectively). Finally, TIMP-1 but no TIMP-2 was associated with the nuclear antigen Ki-67 (p=0.001). These results suggest that TIMP-1 and -2 are expressed in tumoral and stromal tissue in OSCC. TIMP-2 is related to advanced disease, recurrence and poor prognosis.     

Genetic basis of the latex-fruit syndrome: association with HLA class II alleles in a Spanish population

BACKGROUND: The latex-fruit syndrome is a well-defined disorder whose genetic background has not been elucidated. OBJECTIVE: To study the genetic basis of the latex-fruit syndrome. METHODS: In a case-control study, we have investigated a carefully selected group of patients allergic to latex, searching for association between latex-fruit allergy and HLA class I and II genes, HLA-DR functional groups, and markers IL4-R1 and FcepsilonRI-betaca . RESULTS: Seventy-eight patients allergic to latex without spina bifida, 33% of them also allergic to fruits, were included in our protocol. Skin prick test results with both a commercial latex extract and purified hevein were significantly greater in patients allergic to latex and fruit than in patients allergic to latex and not fruit. A cutoff point of >7 mm for commercial latex skin prick test diagnosed latex-fruit allergy with a sensitivity of 66.7% (95% CI, 41.0-86.6) and a specificity of 83.3% (95% CI, 68.6-93.0) in our series of patients. No significant differences were found regarding HLA class I, IL4-R1 , or FcepsilonRI-betaca allele distributions. However, comparison of HLA class II allelic frequencies between patients allergic to latex and fruit and patients allergic to latex and not fruit showed significant associations of latex-fruit allergy with DQB1 *0201 (corrected P value, .001; odds ratio, 7.3; 95% CI, 2.6-20.0), as well as with HLA-DR functional group E (corrected P value, .028; odds ratio, 16.0; 95% CI, 1.9-134.1). When comparing allelic distribution among different subgroups of patients allergic to latex, additional significant associations of latex-fruit allergy with DRB1 *0301 and *0901, and of latex and not fruit allergy with DQB1 *0202, DRB1 *0701 and *1101, were demonstrated. CONCLUSIONS: Latex-fruit allergy is associated with HLA-DQB1 *0201, DRB1 *0301, and *0901, as well as with HLA-DR functional group E, whereas latex-not-fruit allergy is associated with DQB1 *0202, and with both DRB1 *0701 and *1101 alleles.     

New pyrazole derivative 5‐[1‐(4‐fluorophenyl)‐1H‐pyrazol‐4‐yl]‐2H‐tetrazole: synthesis and assessment of some biological activities

The molecular modification and synthesis of compounds is vital to discovering drugs with desirable pharmacological and toxicity profiles. In response to pyrazole compounds' antipyretic, analgesic, and anti‐inflammatory effects, this study sought to evaluate the analgesic, anti‐inflammatory, and vasorelaxant effects, as well as the mechanisms of action, of a new pyrazole derivative, 5‐[1‐(4‐fluorophenyl)‐1H‐pyrazol‐4‐yl]‐2H‐tetrazole. During the acetic acid‐induced abdominal writhing test, treatments with 5‐[1‐(4‐fluorophenyl)‐1H‐pyrazol‐4‐yl]‐2H‐tetrazole reduced abdominal writhing, while during the formalin test, 5‐[1‐(4‐fluorophenyl)‐1H‐pyrazol‐4‐yl]‐2H‐tetrazole reduced licking times in response to both neurogenic pain and inflammatory pain, all without demonstrating any antinociceptive effects, as revealed during the tail flick test. 5‐[1‐(4‐fluorophenyl)‐1H‐pyrazol‐4‐yl]‐2H‐tetrazole also reduced carrageenan‐induced paw edema and cell migration during the carrageenan‐induced pleurisy test. As demonstrated by the model of the isolated organ, 5‐[1‐(4‐fluorophenyl)‐1H‐pyrazol‐4‐yl]‐2H‐tetrazole exhibits a vasorelaxant effect attenuated by Nω‐nitro‐l ‐arginine methyl ester, 1H‐[1,2,4]oxadiazolo[4,3‐alpha]quinoxalin‐1‐one, tetraethylammonium or glibenclamide. 5‐[1‐(4‐fluorophenyl)‐1H‐pyrazol‐4‐yl]‐2H‐tetrazole also blocked CaCl₂‐induced contraction in a dose‐dependent manner. Suggesting a safe toxicity profile, 5‐[1‐(4‐fluorophenyl)‐1H‐pyrazol‐4‐yl]‐2H‐tetrazole reduced the viability of 3T3 cells at higher concentrations and was orally tolerated, despite signs of toxicity in doses of 2000 mg/kg. Lastly, the compounds' analgesic activity might be attributed to the involvement of the NO/cGMP pathway and K⁺ channels observed in the vasorelaxant effect.     

Pharmacological and toxicological evaluations of the new pyrazole compound (LQFM-021) as potential analgesic and anti-inflammatory agents

Chronic inflammation is a world health problem. There is a need to develop new anti-inflammatory and analgesic drugs with improved activity and reduced side effects. In this context, the aim of this study was to evaluate the antinociceptive and anti-inflammatory effects of the pyrazole compound LQFM-021 after acute and sub-chronic administration in rats submitted to a CFA-induced chronic arthritis model, as well as compare the toxicity of this compound to that of dipyrone, given throughout 7 days. Firstly, we observed that acute oral administration of the higher dose (130 µmol/kg) of LQFM-021 reduced paw lifting time (PET) and edema formation. These effects disappeared on the following day, requiring another dose to maintain the effects. This dose also promoted reduction of the polymorphonuclear recruitment in the synovial fluid. In another experiment, both treatments with LQFM-021, 65 µmol/kg twice a day and 130 µmol/kg once a day, produced a progressive and permanent reduction of the PET and edema, also reducing polymorphonuclear recruitment. However, the single treatment with 130 µmol/kg was more effective than the double treatment with 65 µmol/kg. LQFM-021 did not produce toxicity signs. However, dipyrone (130 µmol/kg once a day) promoted erosion of the epithelial cells and decreased mucus in the gastric mucosa. These data indicate that LQFM-021 produced antinociceptive and anti-inflammatory effects in CFA-induced arthritis in rats. These effects occurred in the absence of apparent toxic effects, indicating that the pyrazole compound LQFM-021 may be considered a good prototype for development of new analgesic/anti-inflammatory drug.