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Multidrug therapeutic hybrids constitute a promising proposal to overcome problems associated with traditional formulations containing physical mixtures of drugs, potentially improving pharmacological and pharmaceutical performance. Indomethacin (IND) is a non-selective non-steroidal anti-inflammatory drug (NSAIDs) that acts by inhibiting normal processes of homeostasis, causing a series of side effects, such as gastrointestinal symptoms. Proton pump inhibitors, such as omeprazole (OME), have been used to treat such gastrointestinal tract symptoms. In this work, two new multidrug therapeutic hybrids were prepared (an IND:OME salt and an IND:OME co-amorphous system) by ball mill grinding crystalline IND and OME under different conditions, i.e., liquid assisted grinding (LAG) with ethanol and dry grinding, respectively. The crystalline salt returned to a neutral state co-amorphous system when submitted to ball mill grinding in the absence of solvent (dry grinding), but the reverse process (LAG of the IND:OME co-amorphous system) showed partial decomposition of OME. The IND:OME co-amorphous system showed a higher physical stability than the neat IND and OME amorphous materials (with an amorphous stability longer than 100 days, compared to 4 and 16 h for the neat amorphous drugs, respectively, when stored at dry conditions at room temperature). Furthermore, OME presented a higher chemical stability in solution when dissolved from a salt form than from the pure crystalline form. The dissolution studies showed a dissolution enhancement for IND in both salt (1.8-fold after 8 h of dissolution) and co-amorphous (2.5-fold after 8 h of dissolution) forms. Anti-inflammatory activity using a mice paw oedema model showed an increase of the pharmacological response to IND at a lower dose (∼5mg/kg) for both IND:OME salt (2.8-fold) and IND:OME co-amorphous system (3.2-fold) after 6 h, when compared to the positive control group (IND, administered at 10 mg/kg). Additionally, the anti-inflammatory activity of both salt and co-amorphous form was faster than for the crystalline IND. Finally, an indomethacin-induced gastric ulceration assay in mice resulted in a higher mucosal protection at the same dose (40 mg/kg) for both IND:OME salt and IND:OME co-amorphous system when compared with crystalline OME.

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The study is aimed at investigating if PUFA supplementation could prevent the effects of a short-term HFD on α7nAChR expression and on the severity of sepsis. Swiss mice were used for the in vivo experiments. For the in vitro experiments, we used a microglia cell line (BV-2) and a hepatoma cell line (Hepa-1c1c7) derived from mice. The animals were either fed standard chow, fed a short-term HFD (60%), or given supplementation with omega-3 fatty acid (2 g/kg or 4 g/kg bw) for 17 days, followed by a short-term HFD. Endotoxemia was induced with an intraperitoneal (i.p.) lipopolysaccharide injection (LPS, 5 or 12 mg/kg), and sepsis was induced by subjecting the animals to cecal ligation and puncture (CLP). BV-2 and Hepa-1c1c7 cells were treated with LPS (100 and 500 ng/mL, respectively) for 3 hours. RT-PCR or Western blotting was used to evaluate α7nAChR expression, inflammatory markers, DNMT1, and overall ubiquitination. LPS and HFD reduced the expression of α7nAChR and increased the expression of inflammatory markers. Omega-3 partially prevented the damage caused by the HFD to the expression of α7nAChR in the bone marrow and hypothalamus, decreased the inflammatory markers, and reduced susceptibility to sepsis-induced death. Exposing the BV-2 cells to LPS increased the protein content of DNMT1 and the overall ubiquitination and reduced the expression of α7nAChR. The inflammation induced by LPS in the BV-2 cell decreased α7nAChR expression and concomitantly increased DNMT1 expression and the ubiquitinated protein levels, indicating the participation of pre- and posttranscriptional mechanisms.

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O presente trabalho reporta as características clínicas e cirúrgicas de oito casos de cadelas portadoras de leiomioma vaginal, com histórico de aumento de volume na região perineal, aparecimento de massa pela vulva, disquezia, tenesmo e disúria. As pacientes foram submetidas à cirurgia de episiotomia para ressecção da massa neoplásica, e em quatro casos foi necessária a ovariossalpingo-histerectomia. Porém, uma delas apresentou recidiva, e, no segundo procedimento cirúrgico de exérese de neoformação, o histopatológico diagnosticou leiomiossarcoma. A paciente ainda apresentou mais duas recidivas, até o proprietário optar pela eutanásia. Decorridos quatro meses, as sete cadelas diagnosticadas com leiomioma não apresentaram recidiva, e os proprietários relataram ausência de sinais relacionados com a doença descrita. Conclui-se que a episiotomia para ressecção da massa vaginal e a ovariossalpingo-histerectomia nas cadelas inteiras nos casos de tumores vaginais benignos são tratamentos satisfatórios, com bom prognóstico, ao contrário do leiomiossarcoma.

This study reports the clinical and surgical procedures of eight cases of bitches with vaginal leiomyoma. All animals presented increased volume in the perineal region, and exteriorization of the vulva, dyschezia, tenesmus and dysuria. The patients underwent episiotomy surgery for resection of the neoplastic mass, and ovariosalpingohisterectomy in four cases. However, one had recurrence on the second surgical procedure for removal of neoformation, histopathological diagnosed leiomyosarcoma, the patient also had two more relapses, until the owner chose euthanasia. After four months, the seven dogs diagnosed with leiomyoma showed no recurrence and the owners reported no signs of the disease described. We concluded that episiotomy for vaginal mass resection combined with ovariohysterectomy in cases of benign vaginal tumors have shown satisfactory treatment with good prognostic.

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The cytochrome c nitrite reductase (cNiR) isolated from Desulfovibrio vulgaris Hildenborough is a membrane-bound complex formed of NrfA and NrfH subunits. The catalytic subunit NrfA is a soluble pentahaem cytochrome c that forms a physiological dimer of about 120 kDa. The electron-donor subunit NrfH is a membrane-anchored tetrahaem cytochrome c of about 18 kDa molecular weight and belongs to the NapC/NirT family of quinol dehydrogenases, for which no structures are known. Crystals of the native cNiR membrane complex, solubilized with dodecylmaltoside detergent (DDM), were obtained using PEG 4K as precipitant. Anomalous diffraction data were measured at the Swiss Light Source to 2.3 A resolution. Crystals belong to the orthorhombic space group P2(1)2(1)2(1), with unit-cell parameters a = 79.5, b = 256.7, c = 578.2 A. Molecular-replacement and MAD methods were combined to solve the structure. The data presented reveal that D. vulgaris cNiR contains one NrfH subunit per NrfA dimer.

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En el período comprendido entre Enero de 1991 y Junio de 1996, 89 pacientes con Atresia de esófago (AE) fueron tratados en el Servicio de Cirugía Pediátrica del Hospital Infantil Pequeño Príncipe. Trece pacientes (14,6 por ciento) tenían atresia sin fístula traqueal (tipo I) y 76 pacientes (85,4 por ciento) atresia con fístula traqueoesofágica distal (tipo III). El peso promedio preoperatorio fue de 2.440g (950g a 3.850g) y hubo prevalencia del sexo masculino en la relación de 1,85:1. Las malformaciones asociadas fueron encontradas en 36 pacientes (39,7 por ciento) siendo: cardiovasculares en 11, renales en 4, gastrointestinales en 3 y múltiples en 18 pacientes. Se realizó la anastomosis esofágica término-terminal en 67 pacientes, gastrotomía y cierre de la fístula traqueoesofágica en 6, esofagostomía asociada a gastrotomía en 10, gastrotomía y posterior esofagostomía en 5 y sólo gastrotomía en uno. Cuatro pacientes requirieron reemplazo esofágico tardío de AE tipo I. Las complicaciones postoperatorias de la anastomosis término-terminal fueron: fístula esófago-mediastinal en 3 pacientes, dehiscencia total en 5, estenosis en 18 y recurreccia de la fístula traqueoesofágica en dos. El reflujo gastroesofágico fué encontrado en 15 pacientes. La sobrevida global fué de 60 pacientes (67,4 por ciento)

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En el período comprendido entre Enero de 1991 y Junio de 1996, 89 pacientes con Atresia de esófago (AE) fueron tratados en el Servicio de Cirugía Pediátrica del Hospital Infantil Pequeño Príncipe. Trece pacientes (14,6 por ciento) tenían atresia sin fístula traqueal (tipo I) y 76 pacientes (85,4 por ciento) atresia con fístula traqueoesofágica distal (tipo III). El peso promedio preoperatorio fue de 2.440g (950g a 3.850g) y hubo prevalencia del sexo masculino en la relación de 1,85:1. Las malformaciones asociadas fueron encontradas en 36 pacientes (39,7 por ciento) siendo: cardiovasculares en 11, renales en 4, gastrointestinales en 3 y múltiples en 18 pacientes. Se realizó la anastomosis esofágica término-terminal en 67 pacientes, gastrotomía y cierre de la fístula traqueoesofágica en 6, esofagostomía asociada a gastrotomía en 10, gastrotomía y posterior esofagostomía en 5 y sólo gastrotomía en uno. Cuatro pacientes requirieron reemplazo esofágico tardío de AE tipo I. Las complicaciones postoperatorias de la anastomosis término-terminal fueron: fístula esófago-mediastinal en 3 pacientes, dehiscencia total en 5, estenosis en 18 y recurreccia de la fístula traqueoesofágica en dos. El reflujo gastroesofágico fué encontrado en 15 pacientes. La sobrevida global fué de 60 pacientes (67,4 por ciento)

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The new stentless porcine mitral valve was developed to serve as an anatomically correct substitute for a diseased mitral valve. Extensive acute animal experimentation was performed, and from this the logical sequence for selecting the correct valve size and the specific technique for implanting it were determined. The following are the major steps to successfully implant a mitral stentless valve: First, mitral valve complex analysis must be done to determine the correct procedure to be performed and the feasibility of using the stentless mitral valve. Second, the correct size of stentless mitral valve must be chosen. Third, the papillary muscle anatomy must be assessed to determine the site and number of sutures necessary for securely holding the new origin of the new chordae. Fourth, the papillary muscle sutures must be anchored to the free pericardial edge of the new chordal origin. Fifth, the chordal alignment with both trigonal areas must be perfect. Sixth, the annulus may be sutured using either continuous or interrupted sutures. Perioperative echocardiography, preferably transesophageal echocardiography, should be done in every patient. Although reoperation was necessary in 5 patients (non-valve-related), the results in 74 patients (3 early and 3 late non-valve-related deaths excluded) followed up for at most 26 months (mean, 14 months) have been excellent. The quality of the results obtained in this initial clinical trial has reinforced our current preference for this valve in patients requiring mitral valve replacement. Longer follow-up is required to confirm that these good results continue.

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From March 1992 to August 1993, 50 patients underwent mitral valve replacement with the new heterologous stentless mitral bioprosthesis in our institution. The development of this heart valve substitute, its technique of implantation and the results observed in the first group of 50 patients have had us to review the initial experience. The surgical protocol included an accurate mitral valve complex analysis, adequate valve size selection, attachment of the papillary muscle to the new chordal origin and approximation of the stentless mitral to the patient's annulus. There was one hospital death (2%), not related to the valve or to the technique and four reoperations: two due to endocarditis, one because of a perivalvular leak and one due to a mismatched stentless valve. The late mortality (4%) was not valve-related. The follow-up has shown excellent valve performance with improved left ventricular function in the great majority of the patients. Based on the current analysis, it can be stated that reproducibility of the surgical technique and the excellence of the clinical follow-up may contribute favorably to a better quality of life and longer valve durability in patients requiring mitral heart valve replacement.

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From May 1990 to January 1994, 120 patients underwent aortic valve replacement with the use of the Biocor porcine aortic stentless heart valve (BPASHV). There were 83 male and 3 female patients. The age ranged from 11 seventy-six (76) years with a mean of 36. Eighty-five patients were under 40 years of age. Sixty-four patients underwent their first aortic valve replacement due to rheumatic heart disease, 30 because of prosthetic valve failure and of those: 20 were due to primary tissue failure and in 10 due to prosthetic endocarditis, native aortic bicuspid valve in 11 and senile calcificant aortic valve disease in four. Thirty-three patients had aortic annular related pathology. Their preoperative functional class revealed 61 patients in class III and 59 in class IV. The longest follow-up in this aortic group was 42 months with a mean of 26. The surgical technique used rendered consistent and reproducible results. There was a hospital mortality of six patients (5%). The mortality was not valve related. The hospital morbidity in 14 revealed full recovery of all patients. There were four late reoperations, in two due to recurrent endocarditis and in the last two because of paravalvar leak. There was a late mortality of four patients (non valve related). The follow-up of these patients revealed full competent aortic stentless valve in 97 patients and only minor jet in nine. Most patients are in functional class I and II. The Aortic stentless concept has proven to be outstanding with the use of the Biocor Aortic stentless valve throughout the current follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)

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Beginning March 1992 to February 1994, 65 patients were submitted to mitral valve replacement using the porcine mitral stentless heart valve. This group took in 65 patients, their age ranged from four to 65 with a mean of 26 years. Forty patients were below years of age. The major indication was rheumatic heart disease sequelae in 50 patients, mitral valve endocarditis in six, myomatous degeneration in four and in five previous mitral prosthetic valve was replaced due to tissue failure. The preoperative functional class revealed 35 patients in class III and 30 in class IV. The longest follow-up was 23 months with a mean of 12. The surgical technique used rendered consistent and reproducible results. There was a hospital mortality of two patients or 3.1%. The hospital morbidity revealed full recovery of all patients. There were three patients reoperated because of valve endocarditis in two and in one due to partial dehiscence of the suture at the annular level. All three patients had full recovery after a reoperation. There was a late mortality of two patients, non valve related. The follow-up of these patients revealed full competent stentless mitral valve in 50 patients and in nine minor to mild jets were encountered by color echo-Doppler. Most patients are in functional class I and II. The stenless concept has prove to be outstanding in the mitral position throughout the current follow-up of close to 2 years.(ABSTRACT TRUNCATED AT 250 WORDS)

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