N-Acetylcysteine Attenuates Cisplatin Toxicity in the Cerebrum and Lung of Young Rats with Artificially Induced Protein Deficiency.

Neurotoxicity is a major obstacle in the effectiveness of Cisplatin in cancer chemotherapy. In this process, oxidative stress and inflammation are considered to be the main mechanisms involved in brain and lung toxicity. The aim of the present work was to study the influence of the amount of protein on some oxidative parameters in the brain and lungs of rats treated with Cisplatin (CP) and N-Acetylcysteine (NAC) as neuroprotectors. Four groups of Wistar rats, each containing six animals, were fed with a protein diet at 7% for 15 days. Thereafter, the groups were given either a unique dose of CP® 5 mg/kg or NAC® 5 mg/kg as follows: group 1 (control), NaCl 0.9% vehicle; group 2, CP; group 3, NAC; and group 4, NAC + CP. The animals were sacrificed immediately after the treatments. Blood samples were collected upon sacrifice and used to measure blood triglycerides and glucose. The brain and lungs of each animal were obtained and used to assay lipid peroxidation (TBARS), glutathione (GSH), serotonin metabolite (5-HIAA), catalase, and the activity of Ca+2, and Mg+2 ATPase using validated methods. TBARS, H2O2, and GSH were found to be significantly decreased in the cortex and cerebellum/medulla oblongata of the groups treated with CP and NAC. The total ATPase showed a significant increase in the lung and cerebellum/medulla oblongata, while 5-HIAA showed the same tendency in the cortex of the same group of animals. The increase in 5-HIAA and ATPase during NAC and CP administration resulted in brain protection. This effect could be even more powerful when membrane fluidity is increased, thus proving the efficacy of combined NAC and CP drug therapy, which appears to be a promising strategy for future chemotherapy in malnourished patients.

Oleic acid reduces oxidative stress in rat brain induced by some anticancer drugs.

Oleic acid (OA) is a monounsaturated compound with many health-benefitting properties such as obesity prevention, increased insulin sensitivity, antihypertensive and immune-boosting properties, etc. The aim of this study was to analyze the effect of oleic acid (OA) and some anticancer drugs against oxidative damage induced by nitropropionic acid (NPA) in rat brain. Six groups of Wistar rats were treated as follows: Group 1, (control); group 2, OA; group 3, NPA + OA; group 4, cyclophosphamide (CPP) + OA; group 5, daunorubicin (DRB) + OA; and group 6, dexrazoxane (DXZ) + OA. All compounds were administered intraperitoneally route, every 24 h for 5 days. Their brains were extracted to measure lipoperoxidation (TBARS), H2O2, Ca+2, Mg+2 ATPase activity, glutathione (GSH) and dopamine. Glucose, hemoglobin and triglycerides were measured in blood. In cortex GSH increased in all groups, except in group 2, the group 4 showed the highest increase of this biomarker. TBARS decrease, and dopamine increase in all regions of groups 4, 5 and 6. H2O2 increased only in cerebellum/medulla oblongata of group 5 and 6. ATPase expression decreased in striatum of group 4. Glucose increased in group 6, and hemoglobin increased in groups 4 and 5. These results suggest that the increase of dopamine and the antioxidant effect of oleic acid administration during treatment with oncologic agents could result in less brain injury.

Post COVID-19 Vertigo in a Patient with Hypothyroidism: A Case Report.

Case Summary: Female nurse, 44-years-old with a weight of 127 pounds. She attended our emergency clinic for an urgent care due to post COVID-19 vertigo and anxiety. Her problem began with severe, short-lived attacks of objective-circular type vertigo, accompanied by nausea and vomiting. The symptoms occurred when she assumed a lying position, turn right and sat or stood upright. Interventions: The patient received medical prescription for hypothyroidism, vertigo and anxiety symptoms. Oral route feeding was started and was well tolerated. Outcomes: The patient showed good evolution with the treatment. Currently, she is at home with daily intake of levothyroxine and losartan without complications. Conclusion: The clinical case suggests that in patients with hypothyroidism, COVID-19 infection may trigger and exacerbate vertigo and anxiety.

Tuberculosis of the ribcage by dissemination of Koch bacilli.

INTRODUCTION: Tuberculosis (TB) is an infectious, transmissible and immune disease caused by the Mycobacterium tuberculosis-complex (MTBC). Although osteoarticular tuberculosis (OATB) has been widely described, the ribcage variety remains a rare form. CASE REPORT: A thirteen-month-old male and a twenty-month-old female, both with pain and increased volume of anterolateral left rib cage were described. Physical examination revealed the presence of a soft consistent mass at the level of the 9th and 5th costal arches in the male and female patients respectively. Upon clinical evaluation, tuberculosis was suspected, which was confirmed by X-ray and histopathological studies. After confirmation, the management, based on anti-tuberculosis therapy was started as follows: nine months of anti-tuberculosis therapy for the male patient and fourteen months for the female. The outcomes were favorable for both patients. However, further interventions, consisting of abscess drainage in the male patient and excisional biopsy in the female patient were necessary. With these therapeutic interventions, to date, the patients are without any evidence of active TB.

Pediatric Abusive Head Trauma: Multicentric Experience in Mexico.

Abusive head trauma (AHT) is one of the most severe forms of child abuse due to its morbidity and mortality. However, AHT is still misdiagnosed in developing countries because of its nonspecific clinical picture and limited knowledge of it on the part of physicians. The aim of this study was to describe some characteristics of children with AHT, their families, and caregivers, as well as the clinical data that could serve as signs for its suspicion and the medical-legal resolution of the cases. Children suspect with AHT in emergency rooms in three Mexican hospitals were included after obtaining informed consent from the parents. All information was obtained from the parents by means of a questionnaire and from different clinical and radiological evaluations of the clinical records of the patients. 15 children, with a median age of 5 months and predominantly males (73.33%), were included in the study. 66% reported a history of irritability periods, and most of the patients (73.33%) had more than one habitual caregiver. The diagnosis of AHT was suspected in only 33.33% on admission in the Emergency Services. Acute symptomatology was present in 53.33%, while less severe symptoms were reported in the rest. Special attention should be paid on babies with history of irritable periods. When a child who is previously healthy and suddenly presents with a seizure or cardiorespiratory dysfunction or brought to the hospital dead, the diagnosis of AHT should be considered as a priority.

Oseltamivir induces favorable response on oxidative damage in the brain of rats treated with Bezafibrate.

AIM: The purpose was to measure the effect of Oseltamivir on oxidative biomarkers and dopaminergic and serotonergic systems in brain of rats with induced hypotriglyceridemia by Bezafibrate.Male young Wistar rats were treated as follows: group 1, NaCl 0.9%, (Controls); group 2, Oseltamivir (100 mg/kg); group 3, single dose of Bezafibrate (150 mg/kg); group 4, four dose of Bezafibrate; group 5, single dose of Bezafibrate + Oseltamivir and group 6, four doses of Bezafibrate + Oseltamivir. Drugs were given orally. Triglycerides, Dopamine, 5-hydroxyindoleacetic acid (5-HIAA), Glutathione (GSH), Hydrogen peroxide (H2O2), lipid peroxidation, as well as total ATPase activity were measured using validated methods. RESULTS: Oseltamivir treated animals showed lower GSH and lipid peroxidation levels and an increment in 5-HIAA in the three evaluated brain regions. Treatment with Oseltamivir also reduces H2O2 in the cortex and cerebellum/medulla oblongata. ATPase enzyme increased in these regions in the groups that were administered with Bezafibrate in repeated doses and in combination with Oseltamivir in single dose. Dopamine concentrations decreased in groups treated with Oseltamivir in the three evaluated regions. Also, there was a decrease in dopamine concentrations in the cerebellum/medulla oblongata of the animals treated with the combination of Oseltamivir and Bezafibrate.Innovation and conclusion: Animals with bezafibrate induced hypo-triglyceridemia that received Oseltamivir, either in single or repeated doses, have a higher improvement of their antioxidant activity and also experienced changes in the dopaminergic and serotonergic system in their brain, intending establish the beneficial of joint administration of both drugs in obese patients.

Comparative Bioavailability and Pharmacokinetics Between the Solid Form of Metformin vs a Novel Liquid Extemporaneous Formulation in Children.

Metformin pharmacokinetics in a liquid extemporaneous formulation from commercial tablets was determined in paediatric patients. A randomized, transversal clinical trial was conducted in 34 children and adolescents between 7 and 17 years of age. 17 children were randomized to take metformin in the liquid formulation and, after a 1-week wash period, a 500 mg metformin tablet was administered to them. Blood samples were obtained in Whatman 903® cards at 0, 1, 2, 4, 8, 12 and 24 hours. Extraction was made by direct precipitation with acetonitrile (ACN) and methanol, detection by UPLC and tandem mass spectrometry. The method was accurate, precise, selective and linear from 50 to 1000 ng/mL (r = .9982). Comparative pharmacokinetics, tablet vs formulation, were as follows: Cmax 1503.2 ng/mL vs 1521.4, Tmax 1.5 h vs 2.3, and half-life 8.2 vs 7.5 h. The liquid formulation of metformin showed similar pharmacokinetics to the tablet, and the ratios (90% CI) of geometric mean for metformin were 100.63% (89.13-113.6), 98.08% (88.04-109.2), and 97.52% (84.9-112.01), for Cmax, AUC0-t, and AUC 0-∞, respectively. Pharmacokinetics was determined using WinNonlin Pro 3.1 software. The liquid formulation of metformin showed similar pharmacokinetics to the tablet, allowing a more precise dose adjustment and ease of administration.

A 20-year retrospective study of osteoarticular tuberculosis in a pediatric third level referral center.

PURPOSE: The objective of the present study is to describe the clinical, diagnostic, radiological and therapeutic aspects of osteoarticular tuberculosis (OATB) in patients in a tertiary pediatric hospital, to know if the diagnosis of OATB in pediatrics is a challenge due to its insidious clinical presentation. METHODS: A retrospective, descriptive study of the cases of Tuberculosis (TB) in children was carried out. A total of 159 cases met the condition for the analysis. RESULTS: The most frequent TB modality was extrapulmonary in 85%. Out of this, only 29% was OATB. The mean age was 4.9 years (range 8 months-16 years). Eighty-six per cent of cases received Bacille Calmette-Guérin (BCG) vaccination at birth. Median time of symptoms prior to diagnosis was 8 months. Microbiological confirmation was achieved only in five cases, with a high sensitivity to the antimicrobial treatment. Mycobacterium bovis BCG strain Tokio 172 was confirmed in three cases. Mortality rate was 0% during the time of study CONCLUSION: Our study describes the epidemiological characteristics of OATB cases in Mexican children. This data revealed a high prevalence of bone and joint TB infection. Pediatric OATB should be considered in cases with lytic bone lesions, fever and local pain. In countries with BCG immunization program, M. bovis should not be forgotten as an etiological agent. The low detection rate with one technique approach highlights the urgent need for more sensitive test to diagnose OATB in children.

Consumption of Cooked Common Beans or Saponins Could Reduce the Risk of Diabetic Complications.

Several risks for diseases, such as atherosclerosis, renal diseases, and diabetes, have inextricably been linked with obesity. Nowadays, this health-risk-laden disease is being managed with assorted types of drugs, some of which guarantee modest benefits. The chronic inflammatory effect of obesity has a negative effect in insulin signaling, a situation attributable to insulin resistance that culminates in high blood sugar inputs seen in diseases such as type 2 diabetes and metabolic syndrome. Food such as beans with different bioactive compounds could reduce the risk of diabetic complications. Demand for bean products is growing because of its robust contents of several health-promoting components, eg, saponins. Saponins are characterized by containing lower glucose and cholesterol levels and have been doted with antioxidant activities, as well as anti-inflammatory and anti-diabetic effects. In this writing, the attributes of saponins in providing substantial health and nutritional benefits in humans, as well as in improving and ameliorating diabetic complications, were reviewed.

Case Report: Chest Wall Tuberculosis without Pulmonary Involvement in Three Pediatric Immunocompetent Patients.

Primary rib cage tuberculosis (TB) is an infrequent form of presentation and represents 1% of all cases of osteoarticular TB. We report three cases of children who were previously healthy and who began with swelling of the anterior surface of the rib as initial manifestation of TB. The most important clinical presentations in this series were swelling and pain, with lytic lesions and a soft tissue mass in image studies simulating oncologic pathologies. Because none of the cases had positive epidemiological contact, TB was initially not considered, so the delay in diagnosis from the onset of symptoms was 4, 1, and 2 months, respectively. The diagnosis was made through histomorphological analyses. Treatment was administered during 12, 10, and 9 months. Posttreatment studies did not show any evidence of extrapulmonary TB and until date, the patients remained without relapse or active disease. The findings in our cases illustrate that the diagnosis of chest wall TB should be suspected in all patients from endemic areas who present rib injury.

Insulin plus zinc induces a favorable biochemical response effects on oxidative damage and dopamine levels in rat brain.

The aim was to determine the effect of zinc (Zn) and insulin on oxidative stress and levels of dopamine in brain of rats. Wistar rats were treated either with zinc alone or combined with insulin during 10 days. After the last dose blood glucose was measured. Their brains were extracted to measure H2O2, Ca+2, Mg+2 ATPase, glutathione (GSH), lipid peroxidation (Tbars) and Dopamine. Zn does not possess anti-glycemic effect like Insulin however, it is noticeable that the combination of Insulin plus Zn induces a major glucose reduction (p < 0.0001) than Insulin alone. In cerebellum/medulla oblongata, the groups treated with Insulin and Zn show a significantly increase in dopamine (p < 0.005). Insulin plus Zn reduced GSH level in cortex. Insulin plus Zn reduced level of H2O2 in Striatum and in cerebellum/medulla oblongata. Lipid peroxidation was significantly reduced by the administration of Insulin as in the combination of Insulin and Zn in all regions (p < 0.0001). In cerebellum medulla oblongata, ATPase activity showed an increase only in the group treated with Insulin + Zn. CONCLUSION: These results suggest that the use of insulin plus Zn produce favorable changes on oxidative stress and this as consequence on the levels of dopamine.

The Use of Trace and Essential Elements in Common Clinical Disorders: Roles in Assessment of Health and Oxidative Stress Status.

During the early life, the diet of infants is mainly dominated by milk. Milk is a natural food rich in trace elements focus on essential elements. These elements are very necessary for human metabolism and since they cannot be synthesized by the body, the only source available for the humans to obtain them is by ingestion of natural food. This mini-review aims at updating the knowledge on trace elements, outlining their natural food sources, and their possible implications in common clinical disorders in early and adult life. However, it was found that consumption of food with micronutrients and trace elements may release intracellular compounds and offer oxidative protection or exacerbate oxidative damage to metabolically compromised cells.

Determination of blood dexmedetomidine in dried blood spots by LC-MS/MS to screen therapeutic levels in paediatric patients.

Dexmedetomidine is an imidazole derivative, with high affinity for α2 adrenergic receptors, used for sedation, analgesia and adjuvant anaesthesia. In this study, an analytical method for the quantification of dexmedetomidine in dried blood spots was developed, validated and applied. The drug was extracted from dried blood spot by liquid extraction; the separation was carried out by ultra high-resolution liquid chromatography in reverse phase coupled to tandem mass spectrometry method. An X Select cyano 5 µm HSS column (2.1 X 150 mm, Waters) and a mobile phase composed of 0.1% formic acid: acetonitrile [50:50 v/v], were used. The test was linear over the concentration range of 50 to 2000 pg/mL. The coefficients of variation for the intra and interday trials were less than 15%. The drug was stable under the conditions tested. The method was successfully applied for the quantification of 6 patients, aged 0 to 2 years, with classification ASA I, who underwent ambulatory surgeries, receiving a dose of 1 µg/Kg dexmedetomidine IV. The drug concentrations in the different sampling times were in the range of 76 to 868 pg/mL.

Linezolid-associated optic neuropathy in a pediatric patient with Mycobacterium nonchromogenicum: A case report.

BACKGROUND: Toxic optic neuropathies are alterations of the optic nerve and can be caused by environmental, pharmacological, or nutritional agents. CASE: It is about a 7-year-old male patient, a native of the State of Mexico, Mexico who was diagnosed with cervical mycobacterial lymphadenitis that required management with linezolid. OBSERVATIONS: After 7 months of treatment, visual acuity of the left eye decreased and was accompanied by headache. Neuroinfection and other central nervous system affections were discarded. An adverse effect related to treatment with linezolid was suspected, and linezolid was suspended. The symptoms subsided after discontinuation; however, the patient continued to show decreased visual acuity of the left eye, assessed by his ability to count 2 fingers. The right eye remained unaffected. CONCLUSIONS: Neurotoxicity can be decreased by reducing the total dose of linezolid or by administrating it in an intermittent form. To avoid progression and loss of vision, we suggest frequent periodic ophthalmological evaluation in patients treated with linezolid.

Prescription and consumption of solid oral drugs dispensed as unitary doses in a third level hospital.

BACKGROUND: The knowledge about the pattern of prescription and consumption of solid oral drugs dispensed as unitary doses (UD) in Mexico is sparing. PURPOSE: The aim of this study was to describe the pattern of prescription and consumption of solid oral drugs dispensed as unitary doses (UD) in a third level private hospital of Mexico. A retrospective study of a 60-month period (from 2007 to 2011) was carried out to know the pattern of drugs dispensed as UD in a third level hospital. RESULTS: Among the principal drugs consumed were analgesic, antihypertensive, antibiotic, anti-inflammatory, antiepileptic, and diuretics. The dispensation of drugs per year was as follows: 181 drugs with 85,167 UD in 2007; 199 with 90,519 UD in 2008; 193 with 101,479 UD in 2009; 195 with 100,798 UD in 2010; and 198 with 103,913 UD in 2011. CONCLUSION: The findings confirmed that prescription and consumption of unitary doses in the hospitalization service increased, and revealed the extensive use of analgesics as the principal prescribed drug in this kind of hospital.

Comparative effects of catechin, epicatechin and N-Ω-nitroarginine on quinolinic acid-induced oxidative stress in rat striatum slices.

UNLABELLED: The aim of this work was to compare the effects of catechin (CAT), epicatechin (EPI) and N-ω-l-nitroarginine (L-NARG) on different endpoints of oxidative stress induced by quinolinic acid (QUIN) in a simple tissue preparation, rat striatal slices - with particular emphasis in the glutathione system - in order to provide revealing information on the antioxidant efficacy of these agents in an excitotoxic model. METHODS: Rat striatal slices were incubated for 1h in the presence of 100 µM QUIN and/or 85 µM CAT or EPI, or 100 µM L-NARG. Lipid peroxidation (LP) and the levels of reduced and oxidized glutathione (GSH and GSSG) were determined. RESULTS: The three agents tested completely blocked the QUIN-induced lipid peroxidation and recovered the QUIN-induced altered GSH/GSSG balance. No statistical differences were detected among the protective effects exerted by these antioxidants, suggesting similar efficacy and common antioxidant mechanisms. The antioxidant properties exhibited by these molecules on the excitotoxic model tested herein support an active role of glutathione and prompt their use as therapeutic tools in models of neurodegenerative disorders.

The Role of Dopamine and Its Dysfunction as a Consequence of Oxidative Stress.

Dopamine is a neurotransmitter that is produced in the substantia nigra, ventral tegmental area, and hypothalamus of the brain. Dysfunction of the dopamine system has been implicated in different nervous system diseases. The level of dopamine transmission increases in response to any type of reward and by a large number of strongly additive drugs. The role of dopamine dysfunction as a consequence of oxidative stress is involved in health and disease. Introduce new potential targets for the development of therapeutic interventions based on antioxidant compounds. The present review focuses on the therapeutic potential of antioxidant compounds as a coadjuvant treatment to conventional neurological disorders is discussed.

[Pharmacology for the fetus and the newborn]. / Farmacología del feto y el recién nacido.

During intrauterine life, the fetus can be exposed to a series of substances ingested by the mother, some of which are necessary for her health but detrimental to fetus. The noxious effects of such exposure could present immediately after exposure in the fetus or be manifested at the time of delivery and sometimes weeks after birth. The passage of drugs or nutrients across the placenta depends on some physicochemicals that have the ability to cross the placenta barrier, and thus get in contact with the fetus and produce harmful effects. Considering the physicochemical properties of the substances, the possibility of such compounds to cross the placenta barrier and thence to the fetus can be predicted. Equally, it is important to consider the characteristics of the newborn as an immature being, different from adults, when carrying out pharmacokinetic and pharmacodynamic processes. Based on the latter, it is important to know the behavior or characteristics of the fetus and the newborn in the face of drug management and above all consider the advantages and disadvantages of the use of such drugs for the care of a being yet in development, as is described in this work.

Treatment of pulmonary arterial hypertension using extemporaneous formulation of sildenafil in Mexican children.

Pulmonary arterial hypertension (PAH) is a sickness with high rate of mortality that consists of elevation in pressure of the vessels through which blood flows to the lung. Sildenafil is a therapeutic option for the treatment of PAH in children for the fact that it relaxes the blood vessels and thereby improves pulmonary blood flow. The aim was to analyze the clinical behavior of an extemporaneous formulation of sildenafil as a therapeutic option in children with PAH, twelve children with PAH were studied. The ages and weights of the children ranged from 5 to 15 years and from 13 to 27 kg. All patients received a capsule of 1 mg/kg of sildenafil prepared as extemporaneous formulation in the pharmacology laboratory. Blood levels of sildenafil were analyzed in order to evaluate its availability of developed formulation. Management has derived from physiopathological knowledge and clinical presentations of patients. The mean maximum concentration was 550 ng/ml which is greater than levels reported in adults. Moreover, a therapeutic monitoring of sildenafil was carried out in order to establish an adequate therapeutic range for children and to show that dosages prepared extemporaneously meet the therapeutic needs for the management of PAH. With an average follow-up of once every 2 months, it was found that the evolution of the patients was favorable and without adverse effects that could put their life at risk. The management of PAH with sildenafil prepared as extemporaneous formulation might be considered as a good therapeutic option.

Pulmonary tuberculous: Symptoms, diagnosis and treatment. 19-year experience in a third level pediatric hospital.

BACKGROUND: Pulmonary tuberculosis (PTB) is an infectious disease that involves the lungs and can be lethal in many cases. Tuberculosis (TB) in children represents 5 to 20% of the total TB cases. However, there are few updated information on pediatric TB, reason why the objective of the present study is to know the real situation of PTB in the population of children in terms of its diagnosis and treatment in a third level pediatric hospital. METHODS: A retrospective study based on a revision of clinical files of patients less than 18 years old diagnosed with PTB from January 1994 to January 2013 at Instituto Nacional de Pediatria, Mexico City was carried out. A probable diagnosis was based on 3 or more of the following: two or more weeks of cough, fever, tuberculin purified protein derivative (PPD) +, previous TB exposure, suggestive chest X-ray, and favorable response to treatment. Definitive diagnosis was based on positive acid-fast bacilli (AFB) or culture. RESULTS: In the 19-year period of revision, 87 children were diagnosed with PTB; 57 (65.5%) had bacteriologic confirmation with ZN staining or culture positive (in fact, 22 were ZN and culture positive), and 30 (34.5%) had a probable diagnosis; 14(16.1%) were diagnosed with concomitant disease, while 69/81 were immunized. Median evolution time was 21 days (5-150). Fever was found in 94.3%, cough in 77%, and weight loss in 55.2%. History of contact with TB was established in 41.9%. Chest X-ray showed consolidation in 48.3% and mediastinal lymph node in 47.1%. PPD was positive in 59.2%, while positive AFB was found in 51.7% cases. Culture was positive in 24/79 patients (30.4%), PCR in 20/27 (74.1%). 39 (44.8%) patients were treated with rifampin, isoniazid, and pyrazinamide while 6 (6.9%) received the former drugs plus streptomycin and 42 (48.3%) the former plus ethambutol. There were three deaths. CONCLUSIONS: PTB in pediatric population represents a diagnostic challenge for the fact that clinical manifestations are unspecific and the diagnosis is not confirmed in all cases; that is why clinical suspicion, X-ray findings and PPD are indispensable for opportune start of treatment.