COVID 19 INFECTION IN A PATIENT NEWLY DIAGNOSED WITH HIV/TB COINFECTION – A CASE REPORT

HIV/TB coinfection, COVID 19 with HIV/TB, immune reconstitution inflammatory syndrome (IRIS), TB lymphadenopathy

Canagliflozin reduces the contractile response of isolated heart of normal adult rats / Canagliflozin reduce la respuesta contráctil del corazón aislado de ratas adultas normales

SUMMARY: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) represent a unique class of glucose-declining renal-targeted drugs. The SGLT2i Canagliflozin (CANA) is an anti-hyperglycemic drug that reduces various cardiovascular and renal outcomes in patients with type 2 diabetes mellitus. This study aimed to explore the potential effects of CANA on the isolated healthy adult rat hearts to show if CANA has positive inotropic or cardiac depressant effects via analyzing the amplitude and frequency of cardiac contractions. In isolated normal adult rat hearts, the effects of CANA on cardiac contractility were examined. In a dose-response curve, CANA led to a significant cardiac depressant effect in a dose-dependent manner. This cardiac depressant effect of CANA (10-6 M) was not prevented by atropine. However, this cardiac depressant effect was partially antagonized by both Isoproterenol (10-5 M) and Calcium chloride (10-6 M), suggesting beta-adrenoceptor and calcium channel blocking actions. In addition, the cardiac depressant effect of CANA (10-6 M) was mitigated in part by Nitric oxide synthase inhibitor, L-NAME, suggesting that its action probably depends to some extent on the accumulation of nitric oxide, which decreases the rise of intracellular Calcium. Data from this study demonstrate that CANA has a significant cardiac relaxant effect in isolated hearts of healthy adult rats by different possible mechanisms. This inhibitory effect on cardiac contractility may help improve the diastolic ventricular filling providing a therapeutic potential to help the other cardioprotective mechanisms of CANA in the prevention and treatment of heart failure.

RESUMEN: Los inhibidores del cotransportador de sodio- glucosa 2 (SGLT2i) representan una clase única de fármacos dirigidos a los riñones que disminuyen la glucosa. El SGLT2i Canagliflozin (CANA) es un fármaco antihiperglucémico que reduce varios resultados cardiovasculares y renales en pacientes con diabetes mellitus tipo 2. Este estudio tuvo como objetivo explorar los efectos potenciales de CANA en corazones aislados de ratas adultas sanas para indicar si CANA tiene efectos inotrópicos o depresores cardíacos positivos mediante el análisis de la amplitud y la frecuencia de las contracciones cardíacas. En corazones aislados de ratas adultas normales, se examinaron los efectos de CANA sobre la contractilidad cardíaca. En una curva de dosis-respuesta, CANA condujo a un efecto depresor cardíaco significativo de manera dependiente de la dosis. Este efecto depresor cardíaco de CANA (10-6 M) no fue impedido por la atropina. Sin embargo, este efecto depresor cardíaco fue parcialmente antagonizado tanto por el isoproterenol (10-5 M) como por el cloruro de calcio (10-6 M), lo que sugiere acciones bloqueadoras de los receptores beta adrenérgicos y de los canales de calcio. Además, el efecto depresor cardíaco de CANA (10-6 M) fue mitigado en parte por el inhibidor de la sintasa de óxido nítrico, L-NAME, lo que sugiere que su acción probablemente depende en cierta medida de la acumulación de óxido nítrico, lo que disminuye el aumento de calcio intracelular. Los datos de este estudio demuestran que CANA tiene un efecto relajante cardíaco significativo en corazones aislados de ratas adultas sanas por diferentes mecanismos posibles. Este efecto inhibitorio sobre la contractilidad cardíaca puede ayudar a mejorar el llenado ventricular diastólico proporcionando un potencial terapéutico para ayudar a los otros mecanismos cardioprotectores de CANA en la prevención y tratamiento de la insuficiencia cardíaca.

Cataract and its risk factor among adults residing in South Bihar, India

Background: Cataract is considered as one of the most common causes of visual impairment and the leading cause of blindness in the world. Age related cataract occurs in people above 50 years of age and the its pathogenesis is multifactorial. Therefore, the present study was aimed to assess the prevalence and risk factors for cataract.Methods: Community based cross sectional study was conducted among adults residing at urban areas of South Bihar. The data was collected by interview method, using pre-tested semi-structured questionnaire which contains socio-demographic data, dietary habits, history of diabetes or hypertension, family history of cataract and long-term sun exposure.Results: Among 240 participants, 94 (39.2%) were male and 146 (60.8%) were female. Maximum participants were aged more than 70 years. The prevalence of cataract was 52.1%.Conclusions: The prevalence of cataract was quite high and was significantly associated with age, long term sun exposure and family history of cataract.

Tumor Necrosis Factor Receptor 2: Its Clinical Significance and Clinicopathologic Correlation in acute leukemias.

Objectives: To measure plasma concentrations of Tumor Necrosis Factor Receptor 2 (TNFR2) in patients with acute leukemia, and to correlate the results with clinical features. Material and Methods: Twenty-four patients with acute myeloid leukemia (AML), sixteen patients with acute lymphoblastic leukemia (ALL) and fifteen control subjects were included in the current study. TNFR2 was measured in plasma of all subjects by enzyme-linked immunosorbent assay. Results: Plasma TNFR2 significantly increased in ALL compared to both control and AML cases. Conclusions: TNFR2 may be used as a biomarker for differentiating between AML and ALL patients.

Correlation between the level of vitamin D and Bone mass index in primary osteoporotic patients in Taif, KSA

Osteoporosis [OP] is considered as one of the commonest metabolic bone diseases in orthopedics, characterized by a reduction in bone mass density and micro-architectural deterioration of bone tissue leading to diminished material properties with an increase in bone fragility and susceptibility to minor trauma fractures. The aim of this cross sectional study was to detect the level of vitamin D in patients suffering from primary osteoporosis and to correlate their levels with bone mass index. This work was performed - at the Orthopedic Outpatient Clinic of King Abdul Aziz specialist Hospital, Taif, [KSA] - on 115 patients [77 females and 38 males] fulfilling WHO revised criteria of 1994 for osteoporosis. The mean age of patients was 67.5 +/- 8.2. A medical history was taken and bony pains, fragility fractures, and loss of height, were elicited, with Inclusion criteria in the form of a T-score

Effect of smoking on skin elastic fibers: a morphometric and immunohistochemical analysis

Tobacco smoking is one of the major health problems in the world. This study was conducted to investigate the morphological changes of the dermal elastic tissue of sun-protected skin induced by smoking. Punch biopsies were obtained from the nonexposed skin of 15 smokers and 15 nonsmokers to evaluate the dermal elastic fibers using morphometric analysis and immunohistochemical techniques. Elastic fibers of the reticular dermis were more numerous, thickened and fragmented in smokers than in nonsmokers. Correlations between the cumulative tobacco dose and the morphology of the elastic fibers were highly significant. Immunohistochemical analysis for alpha-1-antitrypsin showed negative cytoplasmic staining for all samples of both smokers and nonsmokers. This study indicates that smoking is one of the risk factors that lead to an increase in elastic fibers of the reticular dermis. This increase is due to elastic tissue degradation rather than by new synthesis, as in solar elastosis. Furthermore, smoking has multiplicative effects on facial ageing and could share, at least in part, a pathophysiological pathway

Long term comparison between single stage Baerveldt and Ahmed glaucoma implants in pediatric glaucoma

To compare the long term intraocular pressure control in pediatric glaucoma patients who underwent single stage Baerveldt glaucoma valve and Ahmed glaucoma valve S2 implantation. A retrospective study was conducted to analyze the data of patients with single stage Baerveldt glaucoma valve and Ahmed valve implantation at Children Hospital Los Angeles. Medical records of patients were reviewed retrospectively and divided into two groups. All cases received single stage valve implantation in which the tube was inserted primarily into the anterior chamber. In cases with Baerveldt implants, the silicone tube was ligated near its plate location with a single absorbable suture. Group 1 included patients with Baerveldt glaucoma implant model BG 101-350, while group 2 included patients with Ahmed valve implant model S-2. Patients' data collected ranged over the period from 2001 to 2008. The minimum follow up period was 6 month; maximum follow up period was 8 years. All patients were below 18 years of age. Success was considered if last postoperative IOP was between 8 and 24 mm Hg [with or without medications], no additional glaucoma surgery after valve implantation, and absence of visually significant complications. Group 1 included 20 cases and group 2 included 11 cases. Long term success rate based on criterion defined was 80% for group 1 [Baerveldt] with average IOP postoperatively on last follow-up of 19.6 mm Hg. In group 2 [Ahmed], average postoperative pressure was 24 mm Hg with 6 out of 11 considered successful based on criterion giving 54.5% success rate. Conclusion: In the long term, single stage Baerveldt implantation appears to control pressure well in pediatric glaucoma

association of metabolic syndrome, insulin resistance and non-alcoholic fatty liver disease in overweight/obese children

To study the prevalence of metabolic syndrome [MS], insulin resistance [IR] and non-alcoholic fatty liver disease [NAFLD] in overweight/obese children with clinical hepatomegaly and/or raised alanine aminotransferase [ALT]. Thirty-three overweight and obese children, aged 2-13 years, presenting with hepatomegaly and/or raised ALT, were studied for the prevalence of MS, IR and NAFLD. Laboratory analysis included fasting blood glucose, serum insulin, serum triglycerides [TG], total cholesterol, high-density lipoprotein cholesterol [HDL-c], low-density lipoprotein cholesterol [LDL-c] and liver biochemical profile, in addition to liver ultrasound and liver biopsy. Twenty patients [60.6%] were labeled with MS. IR was present in 16 [48.4%]. Fifteen [44%] patients had biopsy-proven NAFLD. Patients with MS were more likely to have NAFLD by biopsy [P=0.001]. Children with NAFLD had significantly higher body mass index, waist circumference, ALT, total cholesterol, LDL-c, TG, fasting insulin, and lower HDL-c compared to patients with normal liver histology [P<0.05] and fitted more with the criteria of MS [80% vs. 44%]. IR was significantly more common among NAFLD patients [73% vs. 28%]. There is a close association between obesity, MS, IR and NAFLD. Obese children with clinical or biochemical hepatic abnormalities are prone to suffer from MS, IR and NAFLD

Study of the pituitary-gonadal axis in the proestrus phase in adult female rats subjected to social isolation

Social isolation is a type of stress that might adversely affect sex cycles in both animals and humans. The present study was planned to investigate the pituitary-gonadal axis in the proestrus phase of estrous cycle in adult female rats subjected to social isolation stress for 8 weeks. Twenty Sprague-Dawley adult female rats were divided into two experimental groups: a control group [n = 10] and a socially isolated group [SI, n = 10]. Throughout the study, all rats were monitored for body weight and food intake. After 8 weeks, rats were sacrificed in the proestrus phase of estrous cycle. All rats were examined for final body weight, rectal temperature, hematocrit value, and serum levels of follicle stimulating hormone, luteinizing hormones, prolactin hormone, 17-beta estradiol, and progesterone in addition to histological examination of the ovaries. The results of the present study showed that the SI group had significant decrease in their final body weights and their serum levels of 17-beta estradiol and progesterone, whereas the serum level of prolactin was significantly increased. Histological examination of SI rat ovaries showed fewer growing ovarian follicles and numerous atretic ones compared to control rat ovaries. These findings indicate that social isolation might result in depressed ovarian function in adult female rats

Enhancement of the anti-schistosomal activity of praziquantel by propolis and/or royal jelly

Due to the emergence of resistance to anti-schistosomal drugs, the present study aimed to explore the antischistosomal activity of the natural products Propolis [PP] and Royal Jelly [RJ] to be used alone or in combination with traditional antibilharzial drug such as Praziquantel [PZQ]. Mice received PP at 8 and 16 mg /mouse/day, RJ at 0.3 and 0.6 mg/mouse/day or PZQ at 0.4 mg/mouse/day in addition to their combinations [PP + RJ] or [PP+RJ+PZQ] using the same low and high dose levels before and after cercarial infection. Antischistosomal activity was evaluated by measuring different parameters including either biochemical [SGOT, SGPT, GGT, albumin and bilirubin total and direct], parasitological [Oogram, liver egg load, worm distribution and burden with hatchability study], antischistosomal antibody titre [ASA titer] and histopathological examination of liver tissue. Inspite of their low antischistosomal activity, PP and RJ in a dose dependent manner induced significant liver protection [p < 0.01] as indicated by reversal of the above parameters tested. Similar effects were obtained using combined doses of PP, RJ and PZQ with reduction rate of 67% and 74% of liver enzymes and worm burden; respectively, compared to the reduction rates of the standard drug PZQ alone 48% and 65%, respectively. Thus the anti-schistosomal activity of PZQ could be augmented by the natural products Propolis and /or Royal Jelly

Predictors of non-alcoholic fatty liver disease in obese and overweight Egyptian children: single center study

Pediatric non-alcoholic fatty liver disease [NAFLD] is a global problem which has been increasingly recognized with the dramatic rise in pediatric obesity. The aim of the present study was to identify the clinical, sonographic, and biochemical predictors for NAFLD in obese children. Seventy-six children [2-15 years] were included after an informed consent. All were subjected to full anthropometric assessment [including height, weight, body mass index, subscapular skin fold thickness, waist and hip circumference and calculation of waist: hip ratio], biochemical assessment of liver function tests, lipid profile and insulin: Sixteen patients [21%] had elevated ALT and 6 [7.9%] had elevated AST. Significant dyslipidemia [low HDL-c, high total cholesterol, high LDL-c and triglycerides] and higher insulin resistance were found in obese patients [P<0.01]. The main sonographic findings were hepatomegaly in 20 patients [26.3%] and echogenic liver in 41 patients [53.9%]. Liver biopsy showed simple steatosis in eight cases [24.2%] and non-alcoholic steatohepatitis [NASH] in seven cases [21.2%]. Anthropometric measurements, increased hepatic echogenicty by ultrasound, insulin resistance and lipid profile were good predictors of NAFLD in obese children if assessed together. However, LDL-c was the only sensitive predictor [independent variable] for NAFLD in both uni- and multivariate logistic regression analyses. Dyslipidemia per se is a strong predictor of NAFLD among obese Egyptian children

Genetic polymorphisms in non-alcoholic fatty liver disease in obese Egyptian children

Polymorphisms in the promoter of microsomal triglyceride transfer protein [MTP] lead to decreased MTP transcription, less export of triglyceride from hepatocytes, and greater intracellular triglyceride accumulation. Therefore, functional polymorphisms in MTP may be involved in determining susceptibility to nonalcoholic steatohepatitis [NASH]. The aim of this study is to examine the effect of some genetic influences among a group of obese Egyptian children. A cross-sectional study was conducted on 76 overweight and obese children presenting to the Pediatric Endocrinology Unit, Cairo University Children's Hospital, Egypt, as well as on 20 healthy controls. Anthropometric measurements were taken for all the patients and they underwent clinical examination, ultrasonographic examination of the liver, and liver biopsy when appropriate. Liver functions, blood glucose, serum insulin, C-peptide, and lipid profile were assessed and HOMA-IR calculated. Blood samples from biopsy-proven NASH patients and controls were analyzed by polymerase chain reaction [PCR] and restriction fragment length polymorphism for the -493 G/T polymorphism in the promoter of MTP and the 1183 T/C polymorphism in the mitochondrial targeting sequence of manganese superoxide dismutase [MnSOD]. Eight had biopsy-proven simple steatosis and 7 had NASH. NASH patients had a much higher incidence of the MTP G/G genotype [P = 0.002, CI: 2.9-392] compared with the controls. NASH patients also had a 100% prevalence of the MnSOD T/T genotype. Certain genotypes in MTP and MnSOD are significantly more prevalent among obese children with NASH and may be responsible for such a phenotype

Effect of some plants as functional food supplement on kidney function and structure in experimentally hyperuricemic rats

Hyperuricemia is associated with renal insufficiency and commonly used as a useful early biomarker for chronic kidney diseases. Celery leaves contain a valuable volatile oil and an organic substance called apiol. Celery leaves, chicory and barley are known to have beneficed effect for humans in health and disease. This work was carried out to investigate the effect of dietary fiber supplementation with celery, chicory and barley, alone and in combination, on body weight, food efficiency radio, kidney function and renal histology in experimentally hyperuricemic rats. The experiment was performed using 4 groups of Sprague Dawley rats fed on basal diet supplemented with potassium oxonate [uricase inhibitor] at 2% for 6 weeks to induce experimental hyperuricemia and one group was fed on basal diet only and used as a negative control group. Four experimental diets were prepared by adding the dry powder of celery seeds, chicory leaves or barley grains at 10% or mixture of three plants at 15% [5% from each] to basal diet. The feeding period was 4 weeks. Biochemical analysis of blood urea nitrogen, uric acid and creatinine concentrations in the serum as well as histopathological examination of kidney were performed. Results showed that feeding of celery, chicory and barley mixture at 15% to hyperuricemic rats for 4 weeks increased body weight and improved feed efficiency. It decreased the elevated serum urea nitrogen, uric acid and creatinine concentrations. It also produced an excellent effect on renal histology as it ameliorated the renal damage caused by elevated serum uric acid. The study suggests that dietary intake of plant mixture of celery, chicory and barley at 15% concentration for 4 weeks may be beneficial to patients suffering from hyperuricemia and kidney disease because it improves the function and structure of kidney in hyperuricemic rats

A comparative study of endoscopic ultrasonography versus endoscopic retrograde cholangiopancreatography in children with chronic liver disease.

Background: Endoscopic ultrasonography (EUS) is a less invasive modality and may be equal or superior to endoscopic retrograde cholangiopancreatography (ERCP) in visualizing the biliary tree. Its role and feasibility in children need to be accurately defined. Aim: This study aimed at evaluation of EUS in assessment of children with chronic liver disease (CLD) in comparison with ERCP. Materials and Methods: The present study was carried out between September 2004 and February 2006 on 40 children suffering from CLD. Patients were selected from the Pediatric Hepatology Unit, Cairo University Children's Hospital, Egypt. They were included if they had: sonographic (n = 8) or histopathological evidence of biliary pathology (n = 2); autoimmune hepatitis with high gamma glutammyl transpeptidase (GGT) levels and/or not responding to immunosuppressive therapy (n = 15); cryptogenic CLD (n = 13); neonatal cholestasis with relapsing or persistent course (n = 2). They all underwent EUS and ERCP. Results: Three of six cases with intrahepatic biliary radicle dilatation had Caroli's disease by EUS and ERCP; and the other 3 had sclerosing cholangitis. EUS was equal to ERCP in diagnosis of biliary pathology. However, one false positive case was described to have dilatation and tortuosity of the pancreatic duct by EUS as compared to ERCP. EUS could detect early pancreatitis in 5 cases. One case with cryptogenic liver disease proved to have sclerosing cholangitis by both EUS and ERCP. Conclusion: EUS is an important diagnostic tool for biliary pathology and pancreatitis in children with pancreatico-biliary pathology. ERCP should be reserved for therapeutic purposes.

relationship between placental growth factor, psoriasis and rheumatoid arthritis

Psoriasis is a chronic dermatosis characterized by the presence of heavy neutrophilic infiltrate in both the dermis and epidermis, together with elongated tortuous blood vessels in dermal papillae. Rheumatoid arthritis [RA] is a chronic inflammatory disease characterized by neovascularization and inflammatory cell infiltration within the synovium with associated synoviocyte hyperplasia. Several factors are found to be behind such a type of inflammation, including PIGF. Recognition of how this factor involved in the pathogenesis of psoriasis and RA may be of great help in the development of a new specific therapeutic modality of these disease. Is to study the role of PIGF [serum and synovial] as one of the factors underlying the pathogenesis of psoriasis and rheumatoid arthritis and its correlation with disease severity, duration and activity. Twenty eight RA patients were included in this study, diagnosed according to ACR classification. Forty psoriatic patients were also included in this study, examination and determination of the disease severity using PASI score were done. Measurement of the serum and synovial fluid [SF]PIGF level using ELISA technique was performed and correlation of disease duration and severity with its level was also done. We found that s.PIGF was high in serum of 64% of RA pts and in all synovial fluid samples. There is apositive correlation between the disease severity and its level ,however the correlation between the disease duration and the serum level of P1GF was insignificant.There is a positive correlation between serum and synovial PIGF in rheumatic patients. Serum PIGF [s.PIGF] was high in 92.5% of psoriatic patients and was significantly high in those with severe and moderate disease activity in comparison to those of mild activity and control group. s.PIGF was highly significant correlated with lesion severity. The prevalence of PsA is 35% of psoriatic pts,[male to female 5/2]. 8 patients have oligoarthritis, 6 patient have polyarthritis and DIP involvement .2 of them have spondyloarthropathy. PIGF has a role in the pathogenesis in rheumatoid arthritis and skin lesion of psoriasis and psoriatic arthritis

Nosocomial bacterial infections and antimicrobial resistance among the elderly in geriatric unit of Ain Shams university hospital

Increasing numbers of elderly people are being treated in hospitals and are additionally at particular risk of acquiring nosocomial infections [Nl] with antibiotic-resistant organisms. Prevalence of Nl had been evaluated in this study in all inpatients in Geriatric Medicine Unit, EL Demerdash Hospital of Ain Shams University from March 2004 till September 2006. The association of Nl with intrinsic and extrinsic risk factors was also assessed, as well as the emergence of antibiotic resistant bacterial strains. All specimens were processed by routine methods and their antibiotic sensitivity was performed using the disc diffusion method in accordance with the Clinical and Laboratory Standards Institute [CLSI] guide lines. A total of 107 NIs were found among 100 of the 1202 hospitalized patients [prevalence 8.2% prevalence varied greatly from 3.3% in the internal ward to 14.2% in the ICU]. Respiratory tract as well as urinary tract infections was the most common NIs [43% each]. The most commonly isolated pathogens from ICU and the internal ward were Klebsiella spp.[25%], Candida spp.[12%], Pseudomonas aeruginosa [12%] and methicillin-resistant Staphylococcus aureus [MRSA] [9%]. They were followed by Escherichia coli and Enterobacter spp. [7.5% each], coagulase negative Staphylococci [6%] and Proteus spp. [5%]. Depending on infection site, the most frequent isolates were Klebsiella spp. [41%], MRSA [22%] for respiratory tract infection; Candida spp. [28%], Klebsiella pneumonie [15%], E.coli and Pseudomonas auruginosa [13% each] for urinary tract infection. Our results showed that 61.9% of studied patients with lower respiratory infections were due to endotracheal intubation and 95.2% of patients had urinary catheters and developed urinary tract infections. About 82.0% of the elderly patients were taking antibiotics, for at least 1 month prior to admission, which have contributed to the emergence of highly resistant pathogens among geriatric patients, including methicillin-resistant Staphylococcus aureus, penicillin-resistant Streptococcus spp., and multiple-drug-resistant Gram-negative bacilli and coagulase-negative staphylococcal strains. Colonization and infection with antibiotic resistant bacteria [ARB] is a rising menace in geriatric medicine. Establishing a surveillance system and developing an antibiotic policy provide the basis for antibiotic therapy and controlling antimicrobial resistance

Effect of parsley on both healthy rats and those suffering from acute renal failure

The Present work was conducted to study the effect of parsley on both health rats and those suffering from acute renal failure [ARF] on the nutritional value, the relative ratio of organs to body weight, blood lipid parameters, kidney and liver functions. Thirty male albino rats [Sprague - Dawaley strain] weighting [200 +/- 5 g] divided into three main groups. The first main group [5 rats] fed on basal diet [control negative group]. The second main group [10 rats] divided to two subgroups and fed on basal diets containing 2% and 5% dried parsley. The third main group [15 rats] injected subcutaneous with glycerol [50%, W/v in saline solution] 10 ml/ kg body weight to induce acute renal failure [ARF] and divided into three subgroups, the first fed on basal diet as a [control positive], while second and third subgroups fed on basal diet containing 2% and 5% dried parsley, respectively. The result revealed that, feeding rats, which suffering from ARF on basal diet containing dried parsley [2% and 5%] resulted in improvement on the nutritional value as well as healthy groups, organs weight/body weight relative ratio, serum cholesterol, triglycerides, low density lipoprotein cholesterol [LDL-c], high density lipoprotein cholesterol [HDL-c], very low density lipoprotein cholesterol [VLDL-c], uric acid, urea nitrogen, aspartate amino transferase [AST] and alanine amino transferase [ALT] than the control positive group. It was concluded that parsley at high concentration 5% realized the best effect on lipid profile, kidney and liver functions

Matrix metalloproteinase-8 and tissue Inhibitor of metalloprotinases-2 in tracheal aspirates from ventilated preterm neonates with respiratory distress syndrome

Matrix metalloproteinases [MMPs] are a family of endoproteinases that act in remodeling and destruction of extracellular matrix and basement membrane. An imbalance among their inducers, activators and specific inhibitors is believed 10 generate parenchymal destruction in pulmonary inflammatory diseases. In this study the concentrations of MMP-8 and tissue inhibitor of metalloprotinases [TIMP]-2 were assessed in tracheal aspirate fluids [TAFs] obtained from ventilated preterm neonates during the first postnatal week. The aim was to investigate their possible role in acute inflammatory lung injury associating respiratory distress syndrome [RDS], assess their relation to disease severity and their possible contribution to the development of chronic lung disease [CLD].Clinical and radiographic assessments of respiratory distress were attempted for 90 ventilated preterm neonates who were defined in 3 groups. Group A comprised 32 neonates with RDS, group B constituted 28 neonates with bronchopneumonia while group C included 30 ventilated neonates for extrapulmonary disorders. The median values for fraction of inspired oxygen [FiO[2]] and arterial/alveolar O[2] tension ratio [a/A O[2]] during the first 24 hours of ventilation, as measures of initial severity of respiratory distress, were calculated. TAF samples were collected for measurement of MMP-8 and TIMP-2 levels by ELISA with calculation of MMP-8/TIMP-2 ratio. Clinical outcome was determined in terms of evolution to CLD. A significant increase in MMP-8/TIMP-2 ratio was found in group A as compared to groups B and C [p<0.01, respectively]. Meanwhile, no significant change in MMP-8/TIMP-2 ratio was encountered in group B in comparison to group C [p>0.05]. Among neonates with RDS, MMP-8 was positively correlated to FiO[2] [r=0.64, p<0.01] and was inversely related to a/A O[2] [r=-0.72, p<0.01]. Nineteen [59%] of RDS neonates developed CLD and those were found to have significantly higher MMP-8, MMP-8/TIMP-2 ratio and initial FiO[2] and significantly lower initial a/A O[2] ratio as compared to RDS neonates with no CLD [p<0.01, respectively]. MMP-8 at an optimum cut-off value of 188 ng/mL was the best to predict RDS progression to CLD with a positive predictive value [PPV] of 94.1% and an efficacy of 87.5%. An imbalance between tracheal aspirate MMP-8 and TIMP-2 levels during the early postnatal period could play a role in the acute inflammatory lung injury in neonatal RDS. This imbalance is associated with disease severity and probably contributes to subsequent evolution of CLD. It could also be speculated that early assessment of tracheal aspirate MMP-8 in preterm neonates with RDS might help prediction of later CLD development

Urinary 8-isoprostane and S100B protein concentrations as predictors of hypoxic-ischemic brain damage in asphyxiated neonates

Newborn infants with perinatal asphyxia are prone to the development of hypoxic-ischemic encephalopathy [HIE]. To date, there are no reliable methods for proper identification of infants who are at high risk of HIE after asphyxial insult. We sought to evaluate urinary levels of a lipid peroxidation marker, 8-isoprostane, and a brain specific protein, S100B protein, as non-invasive tools that might help early identification of postasphyxial hypoxic-ischemic brain damage and prediction of its outcome. Thirty term neonates with perinatal asphyxia were evaluated in comparison to 15 matched healthy controls. Urinary concentrations of 8-isoprostane [by ELISA] and S100B protein [by immunoluminometric technique] were determined at first urination [time 1] and repeated in a second sample obtained 24-48 hours postnatally [time 2]. Asphyxiated neonates were clinically monitored for their neurological pattern over the first two postnatal weeks and were subsequently classified as mild [grade I, n=8], moderate [grade II, n=12] and severe [grade III, n=10] HIE. Eleven of these neonates [36.7%] died in the NICU. The results obtained were interpreted in relation to the grade of HIE severity and mortality. Urinary concentrations of 8-isoprostane and S100B protein were significantly higher in asphyxiated neonates at both monitored times, as compared to controls. Levels of both markers were related to the grade of HIE severity being significantly higher in neonates who developed grade II as compared to grade I, while highest levels were found in grade III. A significant increase in urinary 8-isoprostane from time 1 to time 2 was only found in grade III [p<0.05] while S100B protein increased over that time period in grades II and III [p<0.01, respectively]. Survivors showed significantly lower mean level of each marker as compared to those with fatal outcome [p<0.001, respectively], at both monitored times. Diagnostic performance tests revealed that S100B protein was superior to 8-isoprostane, at the two monitored times, for prediction of HIE severity and mortality. At first urination, a cut-off value for S100B protein of 0.3 micro g/L could best predict development of grades II and III HIE with a positive predictive value [PPV] of 100% and an efficacy of 95.5%. Meanwhile, an optimum cut-off value of 6.89 microg/mg creatinine for 8-isoprostane, had a PPV of 90.48% and an efficacy of 88.89% for grades II and III prediction. As predictors of mortality at first urination, an optimum cut-off value for S100B protein of 2.12 micro g/L and for 8-isoprostane of 10.4 micro g/mg creatinine had corresponding PPVs of 90.9% and 90%, respectively and efficacies of 93.3% and 90%, respectively. There was no significant difference in the overall diagnostic performance of each of the two markers either for disease severity or mortality prediction between both monitored times [p>0.05, respectively]. 8-isoprostane and S100B protein levels are increased in urine following birth asphyxia. S100B protein is superior to 8-isoprostane for prediction of both HIE severity and mortality. It could be speculated that measurement of urinary concentrations of these markers, soon after birth, could serve as a clinically useful and relatively simple non-invasive tool to predict the risk for developing HIE following birth asphyxia and its short-term outcome

Endothelin-1 in plasma and airways of preterms with respiratory distress syndrome

The objective of the study was to characterize the relationship between endothelin 1 [ET-1] concentration in plasma and airway of the preterm and the severity of respiratory distress syndrome [RDS] in early postnatal period. 44 preterm neonates were enrolled in two groups. Group I comprised 29 preterm with RDS requiring mechanical ventilation. They were further discriminated into 3 subgroups according to severity of RDS [mild, moderate and severe RDS]. Group II comprised 15 preterms on mechanical ventilation for repeated attacks of apnea of prematurity, matched for gestational and postnatal age with group I and served a reference group. Laboratory investigations included plain chest radiographs, sepsis work -up to rule out infection, arterial blood gas analysis with calculation of arterial alveolar oxygen ratio [a/A O2]. ET-1 concentration was measured in plasma and tracheal aspirates within the first 48 hours of life. Mean plasma ET-1 concentrations were significantly elevated in preterms with moderate and severe RDS as compared to reference preterms [P <0.01 and P <0.001, respectively]. Significant negative correlation existed between plasma ET-1 and each of gestational age and 1 and 5 minutes Apgar scores, whereas significant positive correlation-existed between plasma ET-1 and each of fraction of inspired oxygen [Fi02], mean airway pressure [MAP] and radiographic grading of severity of RDS. On the contrary, mean concentration of ET-1 in tracheal aspirate was significantly lower in preterms with severe RDS as compared to reference preterms [P <0.01]. A significant positive correlation was found between tracheal aspirate ET- 1 levels and 5 minutes Apgar score, while a significant negative correlation existed between tracheal aspirate ET-1 and MAP. Finally, a significant negative correlation was found between plasma and tracheal aspirate levels of ET-1 [P <0.001] in preterms with RDS, as well as in reference preterms. High plasma ET-1 level is associated with more severe RDS and could be a specific marker for pulmonary endothelial injury that may contribute to the development of elevated pulmonary vascular resistance in this setting. Meanwhile, the association of low ET-1 level in the airway with severe RDS may be attributable to limitation of its stimulant effect on surfaetant secretion and /or the development of airway epithelium; hence, rise in airway ET-1 is indicative of improved pulmonary status in the early course of the disease