In silico screening of Annona Muricata L. Leaf constituents and derivatives towards selected targets of Type 2 Diabetes Mellitus

BACKGROUND@#Type 2 diabetes mellitus, or T2DM, is one of the world's most chronic health problems that is linked to numerous deaths and high health care expenses. 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), protein-tyrosine phosphatase 1B (PTP1B) and mono-ADP-ribosyl transferase sirtuin-6 (SIRT6) were among the novel proteins and focus targets of diabetes research. Annona muricata is a commonly used natural remedy for several illnesses, including type 2 diabetes mellitus. However, most of these traditional claims have received few molecular evaluations.@*OBJECTIVES@#This investigated the phytoconstituents and derivatives of the leaves of A. muricata by evaluating their binding profiles towards selected novel T2DM-related protein targets through in silico methods.@*METHODOLOGY@#This study screened the potential lead compounds from the leaves of A. muricata by evaluating the binding energies of the parent compounds and derivatives with the targets compared to the native ligands and known substrates through molecular docking simulations. Additionally, pharmacokinetic, physicochemical properties, and binding interactions were also assessed using several software programs and online databases.@*RESULTS@#Out of the 8 selected parent compounds of Annona muricata, a total of 672 derivatives were designed, tested, and compared against the controls for at least one of the three protein targets. Among these, 280 derivatives exhibited more negative binding energies than controls in each protein target.@*CONCLUSION@#The designed derivatives can be synthesized and further investigated for potential biological effects towards 11β-HSD1, PTP1B, and SIRT6 through in vitro and in vivo experiments.

Preemptive analgesia with ibuprofen increases anesthetic efficacy in children with severe molar hypomineralization: a triple-blind randomized clinical trial

Abstract Molar incisor hypomineralization (MIH) is often accompanied by dental hypersensitivity and difficulty in achieving effective analgesia. Objective: This study evaluated the effectiveness of preemptive analgesia in children with severe MIH, post-eruptive enamel breakdown, and hypersensitivity. Methodology: Ibuprofen (10 mg/kg child weight) or placebo was administered, followed by infiltrative anesthesia and restoration with resin composite. Hypersensitivity was evaluated in five moments. The data were analyzed using the chi-square test, Fisher's exact test, and t-test. Results: Preemptive analgesia provided benefits for the treatment of severe cases of MIH, with an increase in the effectiveness of infiltrative anesthesia and improved patient comfort during the restorative procedure. Conclusion: Preemptive analgesia has shown efficacy in reducing hypersensitivity during restorative dental procedures, evidencing the significance of this study for patients with MIH and hypersensitivity.

Quality of life of HIV+ patients undergoing pharmacotherapeutic follow-up

The influence of pharmacotherapeutic follow-up (PTF) on quality of life was evaluated in 45 HIV+ patients, who were undergoing initial antiretroviral therapy at a specialized care center in northeast Brazil. PTF lasted nine months and quality of life was analyzed at the 1st and 9th meetings using a questionnaire validated for Brazil. The study identified 643 problems related to antiretrovirals and there were 590 pharmaceutical interventions during the PTF. The comparative analysis between the results of the 1st and the 9th meeting was statistically significant for all domains of the questionnaire. For asymptomatic patients, only one domain was statistically significant. For symptomatic patients, six domains were significant. Patients with one year of HIV/AIDS diagnosis had statistically significant differences in five domains. The results suggest that the PTF contributed to improving quality of life, particularly for symptomatic patients and those diagnosed for at least one year - important target groups for Pharmaceutical Treatment.

A influência do seguimento farmacoterapêutico (SFT) sobre a qualidade de vida foi avaliada em 45 pacientes HIV+ assistidos em serviço de atendimento especializado do nordeste brasileiro. O SFT teve duração de 9 meses e a qualidade de vida foi analisada no 1º e 9º encontros através de questionário validado no País. Identificaram-se 643 problemas relacionados aos antirretrovirais e realizaram-se 590 intervenções farmacêuticas durante o SFT. A análise comparativa entre os resultados de qualidade de vida do 1º e 9º encontro foi estatisticamente significativa em todos os domínios do questionário. Quando analisados somente os pacientes assintomáticos, apenas um domínio apresentou significância estatística. Entre os sintomáticos, seis domínios foram significativos. Pacientes com até um ano de diagnóstico de HIV/AIDS apresentaram validade estatística em cinco domínios. Os resultados sugerem que o SFT contribuiu para a melhoria da qualidade de vida dos pacientes, sobretudo dos sintomáticos e/ou com até um ano de diagnóstico, representando grupos-alvo para a prática da Atenção Farmacêutica.

Deltamethrin-impregnated dog collars have a potent anti-feeding and insecticidal effect on Lutzomyia longipalpis and Lutzomyia migonei

Deltamethrin-impregnated PVC dog collars were tested to assess if they were effective in protecting dogs from sand fly bites of Lutzomyia longipalpis and Lu. migonei. A protective effect against Old World species Phlebotomus perniciosus was demonstrated before. Four dogs wearing deltamethrin collars and three dogs wearing untreated collars (not impregnated with deltamethrin) were kept in separate kennels for over eight months in a village on the outskirts of Fortaleza in Cearß, Brazil. Periodically, a dog from each group was sedated, placed in a net cage for 2 h in which 150 female sand flies had been released 10-15 min before. Lu. longipalpis were used 4, 8, 12, 16, 22, 27, and 35 weeks after the attachment of the collars. Lu. migonei were used 3, 7, 11, 15, 22, 26, and 36 weeks after attachment. During 35 weeks, only 4.1 percent (81 of 2,022) Lu. longipalpis recovered from the nets with the deltamethrin collared dogs were engorged, an anti-feeding effect of 96 percent. Mortality initially was over 90 percent and at 35 weeks was 35 percent with half of the sand flies dying in the first 2 h. In contrast, 83 percent of the 2,094 Lu. longipalpis recovered from the nets containing the untreated collared dogs were engorged and the mortality ranged from zero to 18.8 percent on one occasion with 1.1 percent dying in the first 2 h. Similar findings were found with Lu. migonei: of 2,034 sand flies recovered over this period, only 70 were engorged, an anti-feeding effect of 96.5 percent, and mortality ranged from 91 percent initially to 46 percent at 36 weeks. In contrast, engorgement of controls ranged from 91 to71 percent and a mortality ranged from 3.5 to 29.8 percent. These studies show that deltamethrin impregnated collars can protect dogs against Brazilian sand flies for up to eight months. Thus, they should be useful in a program to control human and canine visceral leishmaniasis

Expression of MAGE-1, -2, and -3 genes in gastric carcinomas and cancer cell lines derived from Korean patients

We investigated the expression of MAGE-1, -2, and -3 genes in tissues of 51 gastric carcinomas from Korean patients and in 11 gastric cancer cell lines established in Korea using reverse transcriptase-polymerase chain reaction along with immunohistochemical analyses and DNA sequencing. Among the 51 gastric carcinomas, MAGE-1, -2, and -3 genes were expressed in 16 (31%), 22 (43%), and 17 (33%), respectively, and 31 (60%) expressed at least one of the three genes. In contrast, none of the three MAGE genes were expressed in normal sites of gastric tissue from each cancer patient. Out of 11 gastric cancer cell lines, MAGE-1, -2, and -3 genes were expressed in two (18%), five (46%), and four (36%), respectively. According to the clinicopathological analysis, the expression of any of the three MAGE genes was not significantly correlated with several clinicopathological factors except histologic types (p= 0.067). Immunohistochemical analyses identified positive staining with monoclonal antibodies 77B and 57B specifically against MAGE-1 and -3 proteins, respectively, in nuclei and cytoplasms of cells in mRNA-positive tumor tissue. These findings suggest the possibility as a target for tumor-specific immunotherapy for Korean patients.

Induced tolerance to Schistosoma mansoni antigens modulates periovular granuloma

Immunological tolerance to Schistosoma mansoni antigens induced by oral exposure of neonatal and adult mice to adult worm, soluble egg and polysaccharide antigens conducted to modulated periovular granuloma of infected mice. However the tolerance do not interfere in the infection. The estimative population and subpopulation of lymphocytes in the spleen of tolerized (not infected) animals do not differ from normal animals but Lyt 2.2 reactive lymphocytes to Schistosoma antigens was demonstrated in the tolerized animals.

Gracilis Transplant in the Management of Persistent Prostatic Urethro-rectal Fistula / 대한비뇨기과학회지

This is the report of the use of a gracilis transplant in the correction of a refractory urethro-rectal fistula associated with congenital imperforate anus in a 26 year old male. Three days after birth anoplasty had been performed. Thereafter three further procedures (Swenson type pull-through, direct perineal repair and repeat pull-through with omental interposition) all failed. Success was finally obtained by use of a gracilis transplant introduced via a perineal incision in order to place viable healthy muscle between the urethral closure (performed through perineal incision) and the rectal mucosal closure (performed via posterior prostotomy). Good continence was achieved.

Spontaneous Regression of Multiple Pulmonary Metastases of Advanced Renal Cell Carcinoma: A Case Report / 대한비뇨기과학회지

During an analysis of 27 patients cases of advanced renal cell carcinoma, eleven of which patients had pulmonary metastases. The case of a 53 year old male who underwent spontaneous regression of his lung metastases was found. This patient underwent right radical nephrectomy leaving some gross disease in the right lobe of the liver. Postoperatively regression was noted within 4 weeks and substantial decrease in the size of the metastatic lesions was noted before velban and Depoprovera were instituted 6 weeks after surgery. Complete disappearance of multiple pulmonary metastases was noted on the chest PA 8 weeks after surgery. At the time of the last clinic visit one year postoperatively, the pulmonary metastatic lesions had regressed entirely on the chest PA, leaving only micronodular hilar and Lt. lower lobe lesions on the chest CAT scan.

33 Cases of Advanced Renal Cell Carcinoma, Stage III and IV Follow-up Studies on Management and Survival / 대한비뇨기과학회지

Renal Cell Cancer often presents late, the tumor having extended beyond the site of origin. Therapeutic management under such circumstances is not subject to clear guidelines: whether resectional surgery, radiotherapy, chemotherapy, hormone therapy, or even immunotherapy is of value is not clearly established. The authors have collected a series of 33 cases of Stage III and Stage IV renal cell cancer managed over a 20-year period and have analyzed in order to obtain a better understanding of the natural process of this neoplastic disease, is patterns of spread, its sites of metastasis, and the effectiveness of various therapeutic modalities. Their conclusions: 1. Mean survival time was 24.1 months when radical nephrectomy was employed in comparison with 17.1 months when simple nephrectomy was done and 8.6 months when only a biopsy could be performed. 2. The best results were obtained when combined therapy using radical surgery, radiation and chemotherapy was employed. this resulted in a 35.5 months average survival, as compared with 20.5 months when nephrectomy alone was performed. 3. Presence of a solitary metastasis was associated with an average survival of 25.3 months, whereas two metastatic sites lowered survival to 16.1 months and three sites to 10.7 months. 4. The survival time for Stage III disease was 21 months as compared 17.5 months for Stage IV disease.