Nortriptyline Hydrochloride Solubility-pH Profiles in a Saline Phosphate Buffer: Drug-Phosphate Complexes and Multiple pHmax Domains with a Gibbs Phase Rule "Soft" Constraints.

The solubility of a model basic drug, nortriptyline (Nor), was investigated as a function of pH in phosphate and/or a chloride-containing aqueous suspension using experimental practices recommended in the previously published "white paper" (Avdeef et al., 2016). The pH-Ramp Shake-Flask (pH-RSF) method, introduced in our earlier work (Markovic et al., 2019), was applied. An improved and more detailed experimental design of the Nor solubility measurement allowed us to exploit the full capacity of the pH-RSF method. Complex equilibria in the aqueous phase (cationic and anionic complex formation between Nor and the phosphate) and solid-phase transformations (Nor free base, 1:1 Nor hydrochloride salt, 1:1 and 1:2 Nor phosphate salts) were characterized by a detailed analysis of the solubility measurements using the computer program pDISOL-X. The solid phases were characterized by thermogravimetric analysis, differential scanning calorimetry, powder X-ray diffraction, and elemental analyses. The results of the present investigation illustrate the influence of competing counterions, such as buffering agents, complexing agents, salt coformers, tonicity adjusters, and so forth, on the aqueous solubility of drugs and interconversion of salts. Careful attention given to these factors can be helpful in the formulation of drug products.

The prevalence of comorbidities in patients with multiple sclerosis: population-based registry data.

BACKGROUND: Comorbidities occur frequently in persons with multiple sclerosis (MS). The aim of the present study was to determine the prevalence of the most common comorbidities in the population of MS patients in Belgrade, Serbia. MATERIAL AND METHODS: Data on diagnosed and fully documented comorbidities were taken from the Belgrade MS population registry. The list of explored comorbidities included cardiovascular, malignant, and autoimmune diseases; psychiatric disorders; epilepsy; and type 2 diabetes. In the data analysis, crude, age- and gender-specific, and age-adjusted prevalence was calculated. Additionally, comorbidities were analyzed in patients with various MS phenotypes. RESULTS: The most prevalent group of comorbidities were psychiatric (prevalence (Prev) = 20.59%, 95% CI 19.10-22.17) and cardiovascular comorbidities (Prev = 15.23%, 95% CI 13.93-16.63). The most prevalent single comorbidities were depression (Prev = 11.82%, 95% CI 10.64-13.11) and hypertension (Prev = 11.41%, 95% CI 10.25-12.68). Type 2 diabetes was significantly more prevalent in patients with primary progressive MS compared with the patients with relapsing-remitting and secondary progressive MS (p < 0.001). We found statistically significant positive correlation between number of comorbidities and progression index (p < 0.001). Patients treated with disease-modifying therapies (DMTs) had significantly higher risk of developing comorbidity, after treatment initiation, compared with those who were untreated (p = 0.001). CONCLUSIONS: Our study demonstrated high prevalence of comorbidities in persons with MS, with psychiatric and cardiovascular diseases being the most common. Furthermore, our findings confirmed the association of comorbidities with progression of disability and emphasized their role in treatment decision-making in MS.

White Mustard (Sinapis alba L.) Oil in Biodiesel Production: A Review.

White mustard (Sinapis alba L.) seed oil is used for cooking, food preservation, body and hair revitalization, biodiesel production, and as a diesel fuel additive and alternative biofuel. This review focuses on biodiesel production from white mustard seed oil as a feedstock. The review starts by outlining the botany and cultivation of white mustard plants, seed harvest, drying and storage, and seed oil composition and properties. This is followed by white mustard seed pretreatments (shelling, preheating, and grinding) and processing techniques for oil recovery (pressing, solvent extraction, and steam distillation) from whole seeds, ground seed or kernels, and press cake. Novel technologies, such as aqueous, enzyme-assisted aqueous, supercritical CO2, and ultrasound-assisted solvent extraction, are also discussed. The main part of the review considers biodiesel production from white mustard seed oil, including fuel properties and performance. The economic, environmental, social, and human health risk/toxicological impacts of white mustard-based biodiesel production and use are also discussed.

Solubility-pH profile of desipramine hydrochloride in saline phosphate buffer: Enhanced solubility due to drug-buffer aggregates.

Although solubility-pH data for desipramine hydrochloride (DsHCl) have been reported previously, the aim of the present study was to critically examine the aqueous solubility-pH behavior of DsHCl in buffer-free and buffered solutions, in the presence of physiologically-relevant chloride concentration, using experimental practices recommended in the recently-published "white paper" (Avdeef et al., 2016). The computer program pDISOL-X was used to design the structured experiments (pH-RSF method), to process the data, and to refine the equilibrium constants. Low-to-high and high-to-low pH assays (using HCl, H3PO4, or NaOH to adjust pH) were performed on phosphate-buffered (0.12­0.15 M) saturated solutions of DsHCl in the pH 1.3-11.6 range. After equilibration (stirring 6 h, followed by 18 h stir-free sedimentation), filtration or centrifugation was used for phase separation. Concentration was measured using HPLC with UV/VIS detection. The 2:1 drug-phosphate solubility product (Ksp2:1 = [DsH+]2[HPO42-]) was determined from data in the pH 4-9 region. The free base of desipramine was prepared and used to determine the Ksp1:1 ([DsH+][H2PO4-]) in chloride-free acidified suspension. In addition, phosphate-free titrations were conducted to determine the intrinsic solubility, S0, and the 1:1 drug-chloride solubility product, KspDsHCl = [DsH+][Cl-]. Under the assay conditions, only the phosphate-free solutions showed some supersaturation near pHmax 8.0. In phosphate-containing solutions, pHmax was indicated at higher pH (8.8-9.6). Oils mixed with solids were observed to form in alkaline solutions (pH > 11). Notably, soluble drug-phosphate complexes appeared to form below pH 3.9 and above pHmax in saturated phosphate­containing saline solutions. This was indicated by the systematic pH shift to higher values in the log S-pH curve in alkaline solution than expected from the Henderson-Hasselbalch equation. For pH < 3.9, saturated phosphate-containing saline solutions exhibited elevated solubility, with drug-hydrochloride as the sole precipitate. Salt solubility products, intrinsic solubility, and complexation constants, which rationalized the data, were determined. Elemental, thermogravimetric (TGA), differential scanning calorimetric (DSC), and powder X-ray diffraction (PXRD) analyses were used to characterize the precipitates isolated from suspensions at different pH.

Human serum albumin binding of certain antimalarials.

Interactions between eight in-house synthesized aminoquinolines, along with well-known chloroquine, and human serum albumin (HSA) have been studied by fluorescence spectroscopy. The synthesized aminoquinolines, despite being structurally diverse, were found to be very potent antimalarials. Fluorescence measurements indicate that three compounds having additional thiophene or benzothiophene substructure bind more strongly to HSA than other studied compounds. Competitive binding experiments indicate that these three compounds bind significantly stronger to warfarin compared to diazepam binding site. Fluorescence quenching at three temperatures (20, 25, and 37°C) was analyzed using classical Stern-Volmer equation, and a static quenching mechanism was proposed. The enthalpy and entropy changes upon sulphur-containing compound-HSA interactions were calculated using Van't Hoff equation. Positive values of enthalpy and entropy changes indicate that non-specific, hydrophobic interactions are the main contributors to HSA-compound interaction. Molecular docking and calculated lipophilicity descriptors indicate the same, pointing out that the increased lipophilicity of sulphur-containing compounds might be a reason for their better binding to HSA. Obtained results might contribute to design of novel derivatives with improved pharmacokinetic properties and drug efficacy.

Protective T Cell and Antibody Immune Responses against Hepatitis C Virus Achieved Using a Biopolyester-Bead-Based Vaccine Delivery System.

Hepatitis C virus (HCV) infection is a major worldwide problem. Chronic hepatitis C is recognized as one of the major causes of cirrhosis, hepatocellular carcinoma, and liver failure. Although new, directly acting antiviral therapies are suggested to overcome the low efficacy and adverse effects observed for the current standard of treatment, an effective vaccine would be the only way to certainly eradicate HCV infection. Recently, polyhydroxybutyrate beads produced by engineered Escherichia coli showed efficacy as a vaccine delivery system. Here, an endotoxin-free E. coli strain (ClearColi) was engineered to produce polyhydroxybutyrate beads displaying the core antigen on their surface (Beads-Core) and their immunogenicity was evaluated in BALB/c mice. Immunization with Beads-Core induced gamma interferon (IFN-γ) secretion and a functional T cell immune response against the HCV Core protein. With the aim to target broad T and B cell determinants described for HCV, Beads-Core mixed with HCV E1, E2, and NS3 recombinant proteins was also evaluated in BALB/c mice. Remarkably, only three immunization with Beads-Core+CoE1E2NS3/Alum (a mixture of 0.1 µg Co.120, 16.7 µg E1.340, 16.7 µg E2.680, and 10 µg NS3 adjuvanted in aluminum hydroxide [Alum]) induced a potent antibody response against E1 and E2 and a broad IFN-γ secretion and T cell response against Core and all coadministered antigens. This immunological response mediated protective immunity to viremia as assessed in a viral surrogate challenge model. Overall, it was shown that engineered biopolyester beads displaying foreign antigens are immunogenic and might present a particulate delivery system suitable for vaccination against HCV.

Residual enzymatic activity as a prognostic factor in patients with Gaucher disease type 1: correlation with Zimran and GAUSS-I index and the severity of bone disease.

BACKGROUND: Gaucher disease (GD) is an autosomal recessive disorder produced by mutations in the glucocerebrosidase gene (GBA), causing storage of glucosylceramide in reticuloendothelial cells in multiple organs. Traditionally, the prediction of the phenotype based on the genotype has been reported to be limited. SUBJECTS AND METHODS: We investigated the correlation between the enzymatic residual activity (ERA) and the phenotype at diagnosis of the disease in 45 GD Spanish patients (44 with type I and 1 with type III GD). The genotype involved two of the following previously expressed proteins: c.517A > C (T134P), 1%; c.721G > A (G202R), 17%; c.1090G > T (G325W), 13.9%; c.1208G > A (S364N), 4.1%; c.1226A > G (N370S), 17.8%; c.1246G > A (G377S), 17.6%; c.1289C > T (P391L), 8.5%; c.1448T > C (L444P), 3%; and c.1504C > T (R463C), 24.5%. Recombinant alleles, deletion of 55 bp in exon 9 and 84GG mutation were considered as mutations with no residual enzymatic activity. RESULTS: The ERA showed a statistically significant correlation with chitotriosidase (P < 0.001), age (P < 0.001), spleen size (P < 0.001), 'Zimran's Severity Score Index' (P < 0.01) and the 'Gaucher Disease Severity Score Index-Type I' (P < 0.0001) at diagnosis of the disorder. Previous to any medical intervention, a comparison between the ERA and bone involvement, demonstrated a statistically significant relationship (P < 0.01) between the two variables. CONCLUSIONS: This study data allowed us to define a new criterion for prognostic assessment of the disease at diagnosis, called Protein Severity Index, which expresses the theoretical severity of the genotype presented by patients, according to the corresponding ERA.

Optimization and kinetic modeling of esterification of the oil obtained from waste plum stones as a pretreatment step in biodiesel production.

This study reports on the use of oil obtained from waste plum stones as a low-cost feedstock for biodiesel production. Because of high free fatty acid (FFA) level (15.8%), the oil was processed through the two-step process including esterification of FFA and methanolysis of the esterified oil catalyzed by H2SO4 and CaO, respectively. Esterification was optimized by response surface methodology combined with a central composite design. The second-order polynomial equation predicted the lowest acid value of 0.53mgKOH/g under the following optimal reaction conditions: the methanol:oil molar ratio of 8.5:1, the catalyst amount of 2% and the reaction temperature of 45°C. The predicted acid value agreed with the experimental acid value (0.47mgKOH/g). The kinetics of FFA esterification was described by the irreversible pseudo first-order reaction rate law. The apparent kinetic constant was correlated with the initial methanol and catalyst concentrations and reaction temperature. The activation energy of the esterification reaction slightly decreased from 13.23 to 11.55kJ/mol with increasing the catalyst concentration from 0.049 to 0.172mol/dm(3). In the second step, the esterified oil reacted with methanol (methanol:oil molar ratio of 9:1) in the presence of CaO (5% to the oil mass) at 60°C. The properties of the obtained biodiesel were within the EN 14214 standard limits. Hence, waste plum stones might be valuable raw material for obtaining fatty oil for the use as alternative feedstock in biodiesel production.

Kinetic modeling and optimization of maceration and ultrasound-extraction of resinoid from the aerial parts of white lady's bedstraw (Galium mollugo L.).

In this paper, extraction of resinoid from the aerial parts of white lady's bedstraw (Galium mollugo L.) using an aqueous ethanol solution (50% by volume) was studied at different temperatures in the absence and the presence of ultrasound. This study indicated that ultrasound-assisted extraction was effective for extracting the resinoid and gave better resinoid yields at lower extraction temperature and in much shorter time than the maceration. A phenomenological model was developed for modeling the kinetics of the extraction process. The model successfully describes the two-step extraction consisting of washing followed by diffusion of extractable substances and shows that ultrasound influences only the first step. The extraction process was optimized using response surface methodology (RMS) and artificial neural network (ANN) models. For the former modeling, the second-order polynomial equation was applied, while the second one was performed by an ANN-GA combination. The high coefficient of determination and the low MRPD between the ANN prediction and the corresponding experimental data proved that modeling the extraction process in the absence and the presence of ultrasound using ANN was more accurate than RSM modeling. The optimum extraction temperature was determined to be 80 and 40 °C, respectively for the maceration and the ultrasound-assisted extraction, ensuring the highest resinoid yield of 22.0 g/100g in 4h and 25.1g/100g in 30 min, which agreed with the yields obtained experimentally for the same time (21.7 and 25.3g/100g, respectively).

Introducción y multiplicación in vitro del cultivo de ajo variedad Morado Barranquino

En este trabajo determinamos el efecto de medios de cultivo modificados usando diferentes concentraciones de reguladores de crecimiento (auxinas/citoquininas) para la regeneración y multiplicación in vitro del ajo (Allium sativum L.) variedad Morado Barranquino. En la fase de introducción se cultivó meristemos apicales en tubos de prueba hasta su regeneración y se determinó que el medio MSM + AIB 0,6 mg/L es el más adecuado para la diferenciación y desarrollo del meristemo. Para la multiplicación se utilizaron las microplantas (13 semanas) de la fase de introducción, obteniéndose formación de macollos en cada subcultivo; se logró mejor tasa de multiplicación en el medio MMA + AIA 2,5 mg/L + KIN 5 mg/L y el medio MSM + 2ip 1,5 mg/L con 4,71 y 4.79 respectivamente

We determine the effect of modified culture medium using different growth regulators concentrations (auxins / cytokinins) for regeneration and propagation of in vitro garlic plants (Allium sativum L.) var. ‘Morado Barrranquino. In the introduction stage meristem tips were cultured in test tubes up to regeneration. It was determined that medium MSM + IBA 0.6 mg/L was most suitable for the meristem tip differentiation and development. 13 weeks old microplants obtained on introduction stage were used for multiplication, obtaining the formation of a cluster after each subcultive. The best multiplication ratio was obtained in MMA medium + IAA 2.5 mg/L + KIN 5.0 mg/L and MSM medium + 2iP 1.5 mg/L with 4.71 and 4.79 respectively

Propagación in vitro de Carica papaya var. PTM-331 a partir de meristemos apicales / In vitro propagation of Carica papaya var. PTM-331 from apical meristem

El trabajo consistió en desarrollar un protocolo de propagación in vitro de la variedad de papaya PTM-331 a partir de meristemos apicales, con la finalidad de obtener plántulas vigorosas y libres de enfermedades, empleando la técnica del cultivo de tejidos. Las yemas apicales empleadas fueron obtenidas de plantas cultivadas en invernadero, los cuales fueron usados como explantes para la extracción de meristemos. La mejor diferenciación de meristemos se logró en el medio basal MS suplementado con 0,5 mg.L-1 de BAP, 0,5 mg.L-1 de AIA y 10 mg.L-1 de adenina. La mejor multiplicación se logró con el medio MS suplementado con 0,5 mg.L-1 de BAP, 0,5 mg.L-1 de AIA y 0,3 mg.L-1 de AG3, con un coeficiente de multiplicación de 3,42; mientras que el mejor medio para el enraizamiento fue la combinación del medio MS, 3 mg.L-1 de AIB y 5 mg.L-1 de adenina, donde se obtuvo 83,33% de plantas enraizadas.

An in vitro protocol was develop to propagate variety of papaya PTM-331 from apical meristems, with the objective of obtaining vigorous and disease-free seedlings, using tissue culture techniques. Apical buds were obtained from seedlings cultivated in greenhouse and used as explants for meristem dissection. Meristems were cultured on MS basal medium supplemented with 0,5 mg.L-1 of BAP, 0,5 mg.L-1 of AIA and 10 mg.L-1 of adenine for their differentiation. The best multiplication of explants was achieved with the combination of MS medium supplemented with 0,5 mg.L-1 of BAP, 0,5 mg.L-1 ofAIA and 0,3 mg.L-1 of AG3, where largest seedlings, with more shoots were obtained. The best medium for rooting was the combination of MS, 3 mg.L-1 of AIB and 5 mg.L-1 of adenine, where 83,33% of rooted plants were obtained.

Vólvulo yeyunal incompleto por linfangioma quístico mesentérico / Partial jejunal volvulus due to a mesenteric cystic lymphangioma

Los quistes mesentéricos son tumoraciones benignas poco frecuentes entre las que se encuentran los linfangiomas. Su presentación clínica es variable y pueden producir síntomas agudos debido a complicaciones. Se diagnostican sobre todo en edad pediátrica y su pronóstico, tras exéresis completa, suele ser excelente. Presentamos el caso de una paciente de 15 años con dolor abdominal postprandial y palpación de masa blanda en hipogastrio. Los estudios radiológicos mostraron una gran masa polilobulada de contenido quístico que englobaba un asa de yeyuno con volvulación incompleta. El tratamiento fue la exéresis del quiste y del asa de yeyuno y el diagnóstico anatomopatológico fue de linfangiomaquístico mesentérico. La paciente está asintomática después de más de 3 años de la intervención (AU)

Mesenteric cysts are unusual benign tumours thatinclude lymphangioma. Their clinical presentation is variable and acute symptoms can be produced due to complications. This tumour appears especially in childhood, and its prognosis after surgical removal is excellent. We present the case of a 15 year old female patient with symptoms of postprandial abdominal pain and palpation of smooth mass in hypogastrium. Radiological studies showed a big polilobular mass of cystic substance that included a portion of jejune within complete volvulus. The treatment was the removal of the cyst and a je junal portion and the pathological diagnosis was mesenteric cyst lymphangioma. The patient is asymptomatic more than three years after the intervention (AU)

Paciente con complicación poco frecuente de arteritis de células gigantes / Rare complication in a patient with giant cell arteritis

La arteritis de células gigantes (arteritis de la arteria temporal) es una vasculitis crónica que afecta mayoritariamente a personas de edad avanzada. Aunque se trata de una enfermedad sistémica, se afectan sobre todo las arterias craneales. La complicación más frecuente de esta patología es la pérdida visual. Presentamos el caso clínico de una paciente que padeció varias complicaciones, entre ellas una necrosis lingual, a raíz de serle diagnosticada una arteritis de células gigantes tras iniciar el tratamiento de la misma (AU)

Giant cell arteritis (temporal arteritis) is a chronic vasculitis that usually affects older people. Althought his is a systemic disease, it most often affects the cranial arteries. The most frequent complication of this disorder is visual loss. We report the case of a patient who suffered several rare complications, including tongue necrosis, as a result of being diagnosed with giant cell arteritis following the start of treatment (AU)

Modeling the kinetics of calcium hydroxide catalyzed methanolysis of sunflower oil.

The kinetics of Ca(OH)(2)-catalyzed methanolysis of sunflower oil was studied at a moderate temperature (60 degrees C), a methanol-to-oil molar ratio (6:1) and different catalyst amounts (from 1% to 10% based on oil weight). The methanolysis process was shown to involve the initial triglyceride (TG) mass transfer controlled region, followed by the chemical reaction controlled region in the latter period. The TG mass transfer limitation was caused by the low available active specific catalyst surface due to the high adsorbed methanol concentration. Both the TG mass transfer and chemical reaction rates increased with increasing the catalyst amount.

[Rare complication in a patient with giant cell arteritis]. / Paciente con complicación poco frecuente de arteritis de células gigantes.

Giant cell arteritis (temporal arteritis) is a chronic vasculitis that usually affects older people. Although this is a systemic disease, it most often affects the cranial arteries. The most frequent complication of this disorder is visual loss. We report the case of a patient who suffered several rare complications, including tongue necrosis, as a result of being diagnosed with giant cell arteritis following the start of treatment.

[Partial jejunal volvulus due to a mesenteric cystic lymphangioma]. / Vólvulo yeyunal incompleto por linfangioma quístico mesentérico.

Mesenteric cysts are unusual benign tumours that include lymphangioma. Their clinical presentation is variable and acute symptoms can be produced due to complications. This tumour appears especially in childhood, and its prognosis after surgical removal is excellent. We present the case of a 15 year old female patient with symptoms of postprandial abdominal pain and palpation of smooth mass in hypogastrium. Radiological studies showed a big polilobular mass of cystic substance that included a portion of jejune with incomplete volvulus. The treatment was the removal of the cyst and a jejunal portion and the pathological diagnosis was mesenteric cyst lymphangioma. The patient is asymptomatic more than three years after the intervention.

Kinetics of sunflower oil methanolysis at low temperatures.

The kinetics of the sunflower oil methanolysis process was studied at lower temperatures (10-30 degrees C). The sigmoidal kinetics of the process was explained by the mass transfer controlled region in the initial heterogenous regime, followed by the chemical reaction controlled region in the pseudo-homogenous regime. A simple kinetic model, which did not require complex computation of the kinetic constants, was used for simulation of the TG conversion and the FAME formation in the latter regime: the fast irreversible second-order reaction was followed by the slow reversible second-order reaction close to the completion of the methanolysis reaction. The mass transfer was related to the drop size of the dispersed (methanol) phase, which reduced rapidly with the progress of the methanolysis reaction. This was attributed to the formation of the emulsifying agents stabilizing the emulsion of methanol drops into the oil.

[Epidemiology and tendency of cerebrovascular disease in the National Institute of Neurology and Neurosurgery Manuel Velasco Suárez during the period 1997-2003]. / Epidemiología y tendencia del evento vascular cerebral en el Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez durante el período 1997-2003.

OBJECTIVE: To determine the frequency and behavior of cerebrovascular disease over time in the National Institute of Neurology and Neurosurgery of Mexico City (INNN). METHODS: We reviewed all the clinical charts of the patients with a diagnosis of cerebrovascular disease (CVD) during the period of 1997 to 2003. Simple frequencies, yearly proportion of CVD cases and their tendency during the study period were obtained. The main epidemiological characteristics among the ischemic CVD and hemorrhagic CVD were compared. RESULTS: No tendency to increase was found for this disease. In the analysis by type of CVD, a statistically significant decrease of hemorrhagic CVD was found. The age group in which this disease had the highest frequency was 40 to 59 years and there was a slight predominance of female gender; however this difference was not statistically significant. CONCLUSIONS: Although the frequency of CVD in this study did not show a tendency towards increase, the number of yearly cases in the INNN is high. We consider that even when several risk factors associated to this disease are already known, it is still a major public health problem in the world, considering the enormous consequences for health institutions, society and patients. Therefore it is necessary to continue research on risk factors associated to the development of CVD to influence on its prevention and early diagnosis and treatment.

Epidemiología y tendencia del evento vascular cerebral en el Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez durante el período 1997-2003 / Epidemiology and tendency of cerebrovascular disease in the National Institute of Neurology and Neurosurgery Manuel Velasco Suárez during the period 1997-2003

Objetivo. Determinar la frecuencia y comportamiento de la enfermedad cerebrovascular a través del tiempo en el Instituto Nacional de Neurología y Neurocirugía de la Ciudad de México (INNN). Métodos. Se realizó una revisión de expedientes de los casos diagnosticados con evento vascular cerebral (EVC) durante el período de 1997 a 2003. Se obtuvieron frecuencias simples, se calculó la proporción de los casos de EVC por año y su tendencia a través del período de estudio. Se compararon las principales características epidemiológicas entre los dos tipos de EVC (hemorrágico e isquémico). Resultados. No se encontró una tendencia al incremento para este padecimiento. Se observó una tendencia a la disminución estadísticamente significativa para el EVC hemorrágico. Se presentó con mayor frecuencia en el grupo de 40-59 años de edad con un ligero predominio del sexo femenino; sin embargo, esto no fue estadísticamente significativo. Conclusiones. A pesar de que la frecuencia de EVC en este estudio no mostró una tendencia al incremento, el número de casos que se presentan por año en el INNN es elevado. Se considera un padecimiento que continúa siendo un problema de salud pública en el mundo por las importantes repercusiones que ocasiona, tanto a las instituciones de salud, a la sociedad como a los propios individuos que la padecen. Por ello se considera necesario continuar la búsqueda de factores involucrados en su desarrollo para incidir de manera preventiva con diagnósticos y tratamientos oportunos

Objetive. To determine the frequency and behavior of cerebrovascular disease over time in the National Institute of Neurology and Neurosurgery of Mexico City (INNN). Methods. We reviewed all the clinical charts of the patients with a diagnosis of cerebrovascular disease (CVD) during the period of 1997 to 2003. Simple frequencies, yearly proportion of CVD cases and their tendency during the study period were obtained. The main epidemiological characteristics among the ischemic CVD and hemorrhagic CVD were compared. Results. No tendency to increase was found for this disease. In the analysis by type of CVD, a statistically significant decrease of hemorrhagic CVD was found. The age group in which this disease had the highest frequency was 40 to 59 years and there was a slight predominance of female gender; however this difference was not statistically significant. Conclusions. Although the frequency of CVD in this study did not show a tendency towards increase, the number of yearly cases in the INNN is high. We consider that even when several risk factors associated to this disease are already known, it is still a major public health problem in the world, considering the enormous consequences for health institutions, society and patients. Therefore it is necessary to continue research on risk factors associated to the development of CVD to influence on its prevention and early diagnosis and treatment

The effect of agitation intensity on alkali-catalyzed methanolysis of sunflower oil.

The sunflower oil methanolysis was studied in a stirred reactor at different agitation speeds. The measurements of drop size, drop size distribution and the conversion degree demonstrate the effects of the agitation speed in both non-reaction (methanol/sunflower oil) and reaction (methanol/KOH/sunflower oil) systems. Drop size distributions were found to become narrower and shift to smaller sizes with increasing agitation speed as well as with the progress of the methanolysis reaction at a constant agitation speed. During the methanolysis reaction, the Sauter-mean drop diameter stays constant in the initial slow reaction region, rapidly decreases during the fast reaction period and finally reaches the equilibrium level. Due to the fact that the interfacial area increases, one can conclude that the rate of reaction occurring at the interface will also be enhanced progressively. The "autocatalytic" behavior of the methanolysis reaction is explained by this "self-enhancement" of the interfacial area, due to intensive drop breakage process.