Abnormal Biochemical Changes Research Articles

Predictive Value of Maternal Serum Biomarkers for Preeclampsia and Birth Weight: A Case-Control Study in Chinese Pregnant Women.

In clinical practice, abnormal biochemical changes often occur in women who eventually develop preeclampsia (PE). The study aims to investigate whether maternal serum biochemical markers in the early third trimester can predict PE and neonatal birth weight. A retrospective case-control study was performed on 287 women who subsequently developed PE (mild = 139; severe = 148) and 143 healthy women. Fasting venous blood samples of all gravidas were drawn for routine biochemical markers screening in the early third trimester (28.49 ± 1.63 weeks). Appropriate statistical methods were selected for analysis with SPSS software. (1) The concentrations of plasma triglyceride (TG), low-density lipoprotein cholesterol (LDL), and uric acid (UA) in the severe and mild subgroups of the PE group were significantly higher compared with the respective levels in the normal pregnancy groups (3.90 vs. 4.03 vs. 3.14 mmol/L; 3.41 vs. 3.33 vs. 2.89 mmol/L; 365.42 vs. 318.91 vs. 284.69 μmol/L; p < 0.0001). Serum calcium levels in PE group were significantly lower than those in control group (2.10 vs. 2.18 vs. 2.22 mmol/L; p < 0.0001). (2) By using the receiver operating characteristic curve to estimate the diagnosis rate of screening for PE of each marker, the highest sensitivity appeared by the combination of TG, total cholesterol (TC), LDL, high-density lipoprotein cholesterol (HDL), LDL/HDL, UA, Ca2+, and homocysteine (HCY) (79%). The area under curve (AUC) of UA was 0.70, which was the highest among these eight markers, but the AUC of an eight-marker combination model (0.85) had a better diagnostic indication. (3) In PE, the maximum systolic/diastolic blood pressure was significantly positively correlated with serum UA (r = 0.212/0.205, p < 0.0001); and negatively correlated with serum total calcium (r = -0.193/-0.196, p = 0.001). The neonatal birth weight of PE group had a positive correlation with serum TG levels (r = 0.141, p = 0.017) and serum total calcium levels (r = 0.221, p < 0.0001), and a negative correlation with UA levels (r = -0.265, p < 0.0001). The individual marker really performs terrible in predicting PE. Joint monitoring and evaluation of these parameters may improve the screening efficiency for the prediction of PE and poor fetal growth early.

Cardioprotective and nephroprotective activities of methanolic extracts from Pulicaria somalensis herbs against carbon tetrachloride induced toxicity in rats

Some studies have shown that Pulicaria somalensis (Asteraceae) and related members of this family have long been used in folk medicines and because of the presence of antioxidant activity has an effective role in protection of biomarkers of cardiac and renal dysfunction [1 – 2]. The aim of the present study was to evaluate the protective effects of herbs of Pulicaria somalensis methanolic extract (PSME) on carbon tetrachloride-induced changes in blood biochemical markers of cardio-and nephro-toxicity. For the cardio-protective, biochemical parameters such as LDH, creatinine kinase and albumin, total protein, MDA and NP-SH levels of cardiac tissue were observed. For the nephro-protective, biochemical parameters such as creatinine, sodium, potassium, calcium, urea, uric acid, total protein, MDA and NPSH of nephritic tissue were observed. The results of the present finding showed a significant (P< 0.01 – 0.001) protection of cardiac biochemical markers, at both the doses of PSME (250, 500 mg/kg). The elevated biochemical parameters, LDH, creatine kinase, showed a significant (P< 0.01 – 0.001) reduction toward the normal after administration of PSME. The biochemical parameters such as creatinine, sodium, potassium, calcium, urea, uric acid for nephro-protective was also significantly (P< 0.01 – 0.001) reverse the abnormal biochemical markers changes in the PSME treated animals group. The cardiac and renal protective character was further confirmed by the histopathological examination of their tissues. It is concluded that CCl4-intoxication induced cardiac and renal biochemical markers dysfunction is reduced by pretreatment with PSME.

A comprehensive study of chronic diabetes complications in streptozotocin-induced diabetic rat

Background: The purpose of this study was to provide a reference of chronic diabetes complications by investigating the prolonged hyperglycemia effects on hematological, biochemical and histopathological changes (liver, kidney, spleen, cardiac muscle, adrenal gland, and endocrine pancreas) in diabetic rats induced by streptozotocin. Methods: Ten adult female Sprague-Dawley of uniform age were divided into two Groups. Group 1 was made diabetic by single intraperitoneal injection of streptozotocin (60 mg/kg/bw) whereas Group 2 served as control. After six months, the rats were anaesthetized using pentobarbital. Cardiac puncture was performed to get 3 ml of the blood sample; following 12 hours of an overnight fast. Serum chemistry test and complete blood analysis for lipid profile and blood glucose test; liver and renal functions were performed. Tissue specimens of liver, kidney, spleen, cardiac muscle, adrenal gland, and endocrine pancreas were fixed in 10% formal saline and processed for histological study. Results: There were severe histopathological changes in the affected organs; and the presence of a significant abnormality of lipid profile, liver, and renal functions. Conclusions: The presence of histopathological changes with abnormal biochemical changes is related to the chronic absence of insulin production in the destroyed β-cells which reflect the diabetic complications in a human being.

In vitro protection of biological macromolecules against oxidative stress and in vivo toxicity evaluation of Acacia nilotica (L.) and ethyl gallate in rats.

BackgroundRecently, enormous research has been focused on natural bioactive compounds possessing potential antioxidant and anticancer properties using cell lines and animal models. Acacia nilotica (L.) is widely distributed in Asia, Africa, Australia and Kenya. The plant is traditionally used to treat mouth, ear and bone cancer. However, reports on Acacia nilotica (L.) Wild. Ex. Delile subsp. indica (Benth.) Brenan regarding its toxicity profile is limited. Hence in this study, we investigated the antioxidant capacity and acute toxicity of ethyl gallate, a phenolic antioxidant present in the A. nilotica (L.) leaf extract.MethodsThe antioxidant activity of ethyl gallate against Fenton’s system (Fe3+/H2O2/ascorbic acid) generated oxidative damage to pBR322 DNA and BSA was investigated. We also studied the interaction of ethyl gallate to CT-DNA by wave scan and FTIR analysis. The amount of ethyl gallate present in the A. nilotica (L.) leaf extract was calculated using HPLC and represented in gram equivalence of ethyl gallate. The acute toxicity profile of ethyl gallate in the A. nilotica (L.) leaf extract was analyzed in albino Wistar rats. Measurement of liver and kidney function markers, total proteins and glucose were determined in the serum. Statistical analysis was done using statistical package for social sciences (SPSS) tool version 16.0.ResultsEthyl gallate was found to be effective at 100 μg/mL concentration by inhibiting the free radical mediated damage to BSA and pBR322 DNA. We also found that the interaction of ethyl gallate and A. nilotica (L.) leaf extract to CT-DNA occurs through intercalation. One gram of A. nilotica (L.) leaf extract was found to be equivalent to 20 mg of ethyl gallate through HPLC analysis. Based on the acute toxicity results, A. nilotica (L.) leaf extract and ethyl gallate as well was found to be non-toxic and safe.ConclusionsResults revealed no mortality or abnormal biochemical changes in vivo and the protective effect of A. nilotica (L.) leaf extract and ethyl gallate on DNA and protein against oxidative stress in vitro. Hence, A. nilotica (L.) leaf extract or ethyl gallate could be used as potential antioxidants with safe therapeutic application in cancer chemotherapy.

Topical treatment with Tong-Luo-San-Jie gel alleviates bone cancer pain in rats

Ethnopharmacological relevanceThe herbal analgesic gel Tong-Luo-San-Jie (TLSJ) and its modifications are used in traditional Chinese medicine to manage cancer pain. However, its mechanisms are still unknown. Aim of the studyTo investigate the effects and mechanisms of TLSJ gel on bone cancer pain in a rat model. Materials and methodsA bone cancer pain rat model was established by inoculating Walker 256 rat carcinoma cells directly into the right tibial medullary cavity of Sprague–Dawley rats (150–170g); Phosphate buffered saline (PBS) tibial inoculation was used as control. Cancer-bearing rats were treated twice a day with external TLSJ gel (0.5g/cm2/day) or inert gel control for 21 day (n=10/group). Behavioral tests such as mechanical threshold and paw withdrawal latency (PWL) were carried out. Osteoclastic activities were determined and carboxyterminal pyridinoline cross-linked type I collagen telopeptides (ICTP) and bone-specific alkaline phosphatase (BAP) concentrations were detected with ELISA after treatment. Adverse effects were monitored, and biochemical and histological tests were performed in naïve rats treated with local TLSJ gel for six weeks. ResultsTLSJ treatment significantly restored bone cancer-induced decrease of PWL and mechanical threshold compared to inert gel. It also decreased the level of blood serum ICTP and BAP and inhibited osteoclast activities. No adverse effects or abnormal biochemical and histological changes were detected after TLSJ treatment. ConclusionThe present study shows that TLSJ significantly inhibits bone cancer-induced thermal and mechanical sensitization. It suggests that the gel may be useful in managing cancer pain and that it may act by inhibiting osteoclastic activity.

Prevalence, clinical characteristics and outcome in patients with chronic heart failure and diabetes

Background Chronic heart failure (CHF) and diabetes mellitus portend high morbidity and mortality because of an interrelated pathophysiologic process. This large cohort study aimed to analyze the prevalence, clinical characteristics and long-term outcome of patients with CHF and diabetes. Methods A total of 1119 patients with NYHA functional class II-IV and left ventricular ejection fraction (LVEF) &lt;45% between January 1995 and May 2009 were recruited. Clinical variables, biochemical and echocardiographic measurements were retrospectively reviewed, and composite major cardiac events (MCE) including death, heart transplantation, and refractory heart failure requiring multiple hospitalizations were recorded. Results The prevalence of CHF with diabetes was progressively increased with time (16.9% in 1995-1999; 20.4% in 2000-2004, and 29.1% in 2005-2009) and age (18.5% in &lt;60 years, 26.6% in 60-80 years, and 26.6% in &gt;80 years). Compared with CHF patients without diabetes, those with diabetes had worse cardiac function, more abnormal biochemical changes, and higher mortality. Treatment with glucose-lowering agents significantly improved LVEF and decreased MCE. An elevated serum HbA1c level was associated with large left ventricular end-systolic diameter (P &lt;0.05), decreased LVEF (P &lt;0.01) and reduced survival (P &lt;0.05). Multivariable Logistic regression analysis revealed that after adjustment for confounding factors, NYHA functional class (OR 2.65, 95% CI 1.14-6.16, P=0.024) and HbA1c level ≥7% (OR 2.78, 95% CI 1.00-7.68, P=0.049) were independent risk factors for adverse outcomes in CHF patients with diabetes. Conclusions Prevalence of CHF with diabetes was increasing during past decades, and patients with CHF and diabetes had worse clinical profiles and prognosis. Aggressive anti-CHF and diabetes therapies are needed to improve overall outcomes for these patients.

Thyroid Storm and Lymphocytic Myocarditis

Cardiac failure is the leading cause of mortality in patients with thyroid storm. But the underlying cardiac pathology is unclear. Here, we report a 46-year-old woman who presented with hyperpyrexia and sinus tachycardia subsequent to accidental neck contusion. Her hyperthyroidism was verified by abnormal biochemical changes. Despite vigorous antithyroid treatment including a beta-blocker, glucocorticoid and potassium iodide, the patient eventually succumbed to refractory congestive heart failure in 4 days. Autopsy revealed lymphocytic myocarditis. We propose that lymphocytic myocarditis played a prominent role in her demise.

Paroxysmales nicht-hereditäres Angioödem

Recurrent hypovolaemic shock had been occurring over the last five and four years, respectively, in a 53-year-old woman and a 46-year-old man who had previously been healthy. The attacks were characterized by a tension feeling and sometimes oedema in the limbs, as well as increased thirst. Within a few hours sweating, tachycardia, orthostatic complaints and shock would occur. The woman's systolic blood pressure would fall to 70 mm Hg and the pulse rate rise to 150/min. The man's blood pressure was not measurable by sphygmomanometer during his first attack. Haematocrit rose to 61 and 71.5%, haemoglobin concentration to 20.7 and 21.3 g/dl, respectively. On administration of plasma expanders all abnormal clinical and biochemical changes quickly disappeared, only to recur within weeks or months. The cause of the condition is an increased permeability of the tissue capillaries, while renal, pulmonary and cerebral vessels apparently are unaffected. During ketotifen and tebonin (gingko biloba extract) administration to the man, he required no further hospitalization for nine months, after which he had three severe attacks. The woman had a severe attack of hypovolaemic shock one month on this treatment. The prognosis of capillary leak syndrome is bad.

Therapeutic efficacy of dl-α-lipoic acid on cyclosporine A induced renal alterations

The present study was designed to evaluate the possible beneficial effect of lipoic acid in preventing the renal damage induced by cyclosporine A in rats. Male albino rats of Wistar strain were divided into four groups and treated as follows. Two groups received cyclosporine A by oral gavage (25 mg/kg/body weight) for 21 days to induce nephrotoxicity, one of which simultaneously received lipoic acid treatment (20 mg/kg body weight) for 21 days. A vehicle (olive oil) and a lipoic acid drug control were also included. Cyclosporine A induced renal damage was evident from the decreased activities of tissue marker enzymes (alkaline phosphatase, acid phosphatase, lactate dehydrogenase, aspartate transaminase and alanine transaminase) and decreased activities of ATPases (Na+, K+-ATPase, Ca2+-ATPase and Mg2+ ATPase). An apparent increase in the levels of serum constituents (urea, uric acid and creatinine) and urinary marker enzymes (N-acetyl-beta-D-glucosaminidase, beta-glucosidase, beta-galactosidase, cathepsin-D and gamma-glutamyl transpeptidase) along with significant decline in creatinine clearance were seen in the cyclosporine treated rats, which was reversed upon treatment with lipoic acid. Ultrastructural observations were also in agreement with the above abnormal changes. Lipoic acid effectively reverted these abnormal biochemical changes and minimized the morphological lesions in renal tissue. Hence, this study clearly exemplifies that lipoic acid might be an ideal choice against cyclosporine A induced cellular abnormalities.

Effect of dl-α-lipoic acid on cyclophosphamide induced lysosomal changes in oxidative cardiotoxicity

Cyclophosphamide (CP), one of the widely prescribed antineoplastic drugs can cause fatal cardiotoxicity. The present study is aimed at evaluating the cardioprotective role of lipoic acid in CP induced toxicity. Male albino rats of Wistar strain were divided into four groups and treated as follows: Group I served as control, Group II received a single dose of CP (200 mg/kg b.wt., i.p.), Group III received lipoic acid (25 mg/kg b.wt., orally) for 10 days, and Group IV received CP immediately followed by lipoic acid for 10 days. In CP administered rats, the levels of protein carbonyl and 8-hydroxy-2-deoxyguanosine were increased significantly ( P < 0.001) indicating oxidative changes in the heart tissue. The activities of lysosomal acid hydrolases, β-Glu, β-Gal, NAG, Cat-D and ACP increased significantly ( P < 0.001) in the serum as well as in the heart tissue after CP administration. An increase in hydroxyproline was observed in CP induced rats. Lipoic acid effectively reverted these abnormal biochemical changes to near normalcy. These observations highlight the protective role of lipoic acid in CP induced cardiotoxicity.

Protective effect of lupeol and its ester on cardiac abnormalities in experimental hypercholesterolemia

Hyperlipidemia is a major risk factor for the premature development of coronary heart disease and it has been shown to increase the incidence of myocardial ischemia and cardiac events. Pentacyclic triterpenes possess antiatherosclerotic, antioxidant, anti-inflammatory and cytoprotective effects. To study the effect of plant derived triterpene, lupeol and its ester lupeol linoleate, on lipid status and biochemical changes on heart tissue, male albino Wistar rats were fed high-cholesterol diet (normal rat chow supplemented with 4% cholesterol and 1% cholic acid; HCD) for 30 days. There was a significant ( p < 0.001) increase in the levels of total cholesterol, triglycerides and phospholipids along with augmented activities of lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase in the heart tissue. Triterpenes treatment reduced the above alterations produced in hypercholesterolemic rats. The transmembrane enzymes, namely Na +, K +-ATPase, Ca 2+-ATPase and Mg 2+-ATPase showed a decrease in their activities. Triterpenes treatment reversed these levels, prevented the hypertrophic cardiac histology and restored the normal ultrastructural architecture. In conclusion, lupeol and lupeol linoleate intervention minimized the lipid abnormalities and abnormal biochemical changes induced by HCD fed rats. This shows that triterpenes possess cardioprotective effects which will be beneficial in hypercholesterolemic condition. Out of these two triterpenes tested, lupeol linoleate appeared to be even more effective than lupeol.

Beneficial role of sulfated polysaccharides from edible seaweed Fucus vesiculosus in experimental hyperoxaluria

Sulfated polysaccharides from marine algae are known to possess numerous properties of pharmacological importance. The present study is an attempt to evaluate the efficacy of the sulfated polysaccharides from edible seaweed, Fucus vesiculosus in ameliorating the abnormal biochemical changes in experimental hyperoxaluria. Two groups of male albino rats of Wistar strain (140 ± 20 g) received 0.75% ethylene glycol for 28 days to induce hyperoxaluria, and one of them received sulfated polysaccharides (fucoidan from F. vesiculosus, 5 mg/kg b.wt., s.c.) treatment, commencing from the 8th day of the experimental period. One group was maintained as a control group and another group served as a drug control, which received only sulfated polysaccharides. Incongruity in the renal tissue enzymes (ALP, β-Glu and γ-GT) were observed during hyperoxaluria along with an increased activity of oxalate metabolizing enzymes like LDH, GAO and XO. These changes were reverted to near normalcy with sulfated polysaccharide administration. Alterations were observed in the activities/levels of tissue enzymic (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione S-transferase and glucose-6-phosphate dehydrogenase) and non-enzymic (reduced glutathione, ascorbate and α-tocopherol) antioxidants, along with high malondialdehyde levels in the hyperoxaluric group. However, normalized lipid peroxidation status and antioxidant defences were noticed with sulfated polysaccharide administration. Biochemical discrepancies observed in hyperoxaluria disrupt membrane integrity, favouring a milieu for crystal retention. Advocation of sulfated polysaccharides enhanced the antioxidant status, thereby preventing membrane injury and alleviating the microenvironment favourable for stone formation.

Cytoprotective role of DL-α-Lipoic acid in cyclophosphamide induced myocardial toxicity

Cyclophosphamide (CP), a potent antitumor drug is known to cause severe cardiotoxicity. The present study is aimed at evaluating the cardioprotective role of lipoic acid in CP induced toxicity. Male albino rats of Wistar strain were divided into four groups and treated as follows: Group I served as control, Group II received a single dose of CP (200 mg/kg b.wt., i.p.), Group III received lipoic acid (25 mg/kg b.wt., orally) for 10 days, Group IV received CP immediately followed by lipoic acid for 10 days. In CP administered rats, the activities of tissue marker enzymes (creatine phosphokinase, lactate dehydrogenase, aspartate transaminase and alanine transaminase) were significantly (p<0.001) reduced, ATPases suffered loss in enzyme activity and thiols were depleted. Histopathological observations were also in agreement with the above abnormal changes. Lipoic acid effectively reverted these abnormal biochemical changes and minimized the histopathological lesions in heart. These observations highlight the protective role of lipoic acid in CP induced cardiac injury.

Cardiotoxicity of doxorubicin/paclitaxel combination in rats: effect of sequence and timing of administration.

The higher incidence of cardiotoxicity of doxorubicin (DOX)/paclitaxel (PTX) combination compared with DOX alone remains to be a major obstacle against effective chemotherapeutic treatment. We investigated the effect of sequence and time interval between administration of both drugs on the severity of cardiotoxicity of the combination. Male Wistar rats were divided into seven groups. DOX was administered intraperitoneally (i.p.) at a single dose of 5 mg x kg(-1) every other 2 days, 2 doses per week for a total cumulative dose of 20 mg x kg(-1). PTX was administered by an i.p. route at a dose of 20 mg x kg(-1) every other 2 days. Both drugs were injected either alone or sequentially in combination. In one case, DOX preceded PTX by 30 min and 24 h and in the other case, PTX preceded DOX by 30 min and 24 h. Cardiotoxicity was evaluated by both biochemical and histopathological examination, 48 h after the last DOX dose. DOX-induced cardiotoxicity was manifested by abnormal biochemical changes including marked increases in serum creatine phosphokinase isoenzyme (CK-MB), lactate dehydrogenase (LDH), glutathione peroxidase (GSH-Px), and aspartate aminotransferase (AST) activity levels. Myocardial tissue from DOX-treated rats showed significant increases in malondialdehyde (MDA) production and total nitrate/nitrite (NOx) levels, parallel with depletion of "endogenous antioxidant reserve," including GSH contents and GSH-Px activity level. PTX treatment produced significant changes in the biochemical parameters measured by a lower magnitude than those changes produced by DOX alone. Combination of both drugs resulted in aggravation of DOX-induced cardiotoxicity regardless the sequence and time interval between administration of either drug. Administration of PTX 30 min and 24 h after DOX treatment showed exaggeration of combination-induced cardiotoxicity compared with the reverse sequence. This exacerbation was manifested by much more pronounced changes in serum and cardiac tissue parameters measured. Histopathological examination of ventricles of rat's heart revealed that DOX treatment produced myo-cytolysis and myocardial necrosis. Administration of PTX following DOX treatment showed extensive myocardial necrosis compared with those rats treated with either DOX alone or the reverse sequence of administration. Moreover, rats treated with PTX 24 h after DOX treatment showed exaggeration of the combination-induced cardiotoxicity. In conclusion, PTX might synergistically aggravate DOX-induced cardiotoxicity. The effect might be much more pronounced with those rats treated with PTX 24 h after DOX treatment.

Experimental Study of Subchronic Toxicity of Lanthanum Nitrate on Liver in Rats

Wistar rats were divided into six groups, which were given La (NO(3))(3) at 20.0, 10.0, 2.0, 0.2, and 0.1 mg/kg, and the control group, which was given physiological saline, respectively, for six months. Pathological changes of liver were observed via light microscopy and transmission electron microscopy. Glutamic-oxalacetic transaminase, glutamic-pyruvic transitanase, gamma-glutamyl transferase, and alkline phosphatase activities in the serum were measured. Superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and malondialdehyde of liver were determined. The metabolic accumulation of lanthanum in rat liver was investigated via inductively coupled plasma mass spectrometry. Results showed no abnormal biochemical changes. In the group of 20.0 mg/kg La(NO(3))(3), there were loss of weight, decrease of glycogen in the hepatocytes, denser matrix of the mitochondria, and deformation of the nuclei of some hepatocytes with different degrees and infiltration of inflammatory cells in the portal area. The higher was the dose, the higher was the number of bodies contain high electronic dense gravel-like granules, and secondary lysosomes with dense bodies were observed. In the group fed 0.1 mg/kg La(NO(3))(3), intracellular glycogen showed an increasing tendency, particularly increased animal growth and increased activities of SOD and GSH-Px. The content of La in the liver increased regularly with increase in dose and time of administration. The results further proved that low-dose La(NO(3))(3) produced some specific biologic effects. This study illustrated the influence of La(NO(3))(3) on rat liver at cellular and subcellular levels and it provides an experimental basis for the purpose of setting a reasonable standard for safely utilizing rare earth elements.

Contractility in vitro and mitochondrial response in small and large rabbit bowel after anastomosis.

Leakage of a large bowel anastomosis remains the most serious postoperative complication in gastrointestinal surgery. In a recent experimental study we found that surgically induced hypoxia resulted in more derangement of a variety of biochemical markers in the large bowel (LB) than in the small bowel (SB). We explored the question of whether spontaneous and agonist-induced contractility of SB and LB muscle strips was influenced by surgical procedures and how contractility was related to energetic oxidative metabolism capacity in smooth muscle mitochondria. Sixty male New Zealand rabbits were operated on under general anesthesia. Segments of ileum and colon were resected from each rabbit, and an end-to-end anastomosis was constructed. A representative subset of segments from SB (n = 14) and LB (n = 14) at time 0 was used as controls. Tracts containing an anastomosis were resected at days 2, 7, and 14 after operation. At each time point, 20 segments adjacent to the anastomosis of both SB and LB were used for tensiometric and biochemical studies. Tensiometric studies demonstrated modifications in the smooth muscle function at both the acute and chronic stages with intestinal inflammation that may contribute to surgical stress-associated abnormal motility. Biochemical data showed that the respiratory capacity of the resected LB was more impaired than that of the SB. In both SB and LB, changes in respiratory activity preceded tensiometric changes. Thus abnormalities of contractility after surgical stress are more evident in LB than SB in segments adjacent to the anastomoses. This could be the consequence of abnormal biochemical changes, as adenosine triphosphate (ATP) is required for membrane potential maintenance, calcium homeostasis, and actin-myosin interactions.

The preventive role of deferoxamine against acute doxorubicin-induced cardiac, renal and hepatic toxicity in rats

The iron chelating activity of deferoxamine (DFO) has been exploited to obtain protection against the peroxidative damage in rat heart which was induced by the administration of an acute dose of doxorubicin (DXR, 25 mg kg−1, i.v.). The peroxidative lesions were evaluated both biochemically and histopathologically, 48 h after DXR administration. Abnormal biochemical changes including a marked increase in the levels of serum creatine kinase isoenzyme (CK-MB), and lactate dehydrogenase (LDH), as well as elevated serum creatinine, blood urea nitrogen and transaminases (ALT and AST) levels were observed. Myocardial tissue from DXR treated rats showed a marked increase in malondialdehyde (MDA) production and depletion of reduced glutathione (GSH) contents. Similar results were also observed in both kidney and liver tissues. Pretreatment of rats with DFO, given i.p. 30 min prior to DXR injection, substantially reduced the peroxidative damage in the myocardium, hepatic and renal tissues and markedly lowered the serum CK-MB, LDH and the other biochemical variables. The protective effects obtained by DFO administration, however, were not complete and did not reach those of the control group. The significant protection against DXR-induced cardiomyopathy by DFO was evident from the histopathological findings observed by light microscopy. DFO at a dosing level equivalent to 10-fold of that of DXR was useful to obtain protective effects. Higher DFO dosing levels did not, however, show more improvement in the DXR-induced cardiotoxicity and at the same time exhibited hepatoxicity which was confirmed by microscopical examination. These results strongly suggest that DFO protects against acute DXR-induced cardiotoxicity in a dose-dependent manner with recognizing the presence of mild DFO-related biochemical and cytological hepatic toxicity.

Morphological characteristics of Impatiens flanaganiae Hemsl. grown under different light conditions

Impatiens flanaganiae Hemsl. is a rare plant which preferentially grows in shady conditions and exhibits strong apical dominance. The morphological plasticity of I. flanaganiae in response to light intensity in laboratory conditions was investigated. Unbranched plantlets of I. flanaganiae propagated from tubers were exposed to three light regimes: 30, 55 and 280 microeinsteins m− 2 sec− 1 for a period of seven weeks. Plants grown under lower light intensity (30–55 microeinsteins m− 2 sec− 1) developed long unbranched stems about 65 cm in length and fewer leaves with a large leaf area. In contrast, reduced stem extension (up to 35 cm) and multiple lateral branches were observed in plants exposed to higher light intensity (280 microeinsteins m− 2 sec− 1). A significant increase (at 5% level) in the number of leaves in plants from this variant was found to be inversely proportional to the leaf area. Extended exposure of the plants to higher light intensities seems to be stressful and resulted in abnormal biochemical and morphological changes such as chlorosis, necrosis and curling of the leaves. The strong increased premium on lateral growth of I. flanaganiae, induced by light intensity of 280 microeinsteins m− 2sec− 1 resulted in a greater number of lateral branches which were found to be suitable for its rapid and more efficient propagation in vivo by cuttings or in vitro by shoot tip culture.

Hepatic injury during ketoconazole therapy in patients with onychomycosis: A controlled cohort study

To evaluate the incidence, severity, and course of ketoconazole- associated hepatic injury, 211 patients with onychomycosis were randomized by a ratio of 2:1 to receive either ketoconazole (137 patients) or griseofulvin (74 patients). All of them were seronegative for hepatitis B surface antigen (HBsAg) and anti-hepatitis C virus (HCV) and had no biochemical abnormality before therapy. The two groups were comparable in age, sex, and pretherapy liver biochemical tests. Liver biochemical tests were followed up biweekly for 3 months, and then at monthly intervals during the remaining course of therapy. No biochemical abnormality or hepatic injury was found in patients during griseofulvin treatment. Of the patients treated with ketoconazole, 24 (17.5%; 95% confidence interval [CI], 11.1% to 23.9%) showed asymptomatic transaminase elevation. Ketoconazole was discontinued immediately after overt hepatitis developed in another 4 patients (2.9%; 95% CI, 0.1% to 5.7%) who did not succumb to hepatic decompensation. The abnormal biochemical changes in patients with overt hepatitis returned to normal after discontinuing ketoconazole. Elderly patients were more prone to develop overt hepatitis. In patients with asymptomatic liver injury, the abnormal biochemical changes gradually returned to normal despite continuing ketoconazole therapy. The results of this cohort study suggest that ketoconazole-induced overt hepatitis is more common than previously believed and that transient subclinical injury is much more common than overt hepatitis. Therapy with ketoconazole may be continued with caution in the absence of symptoms and/or hyperbilirubinemia, but should be discontinued if overt hepatitis occurs.(Hepatology 1997 Jan;25(1):103-7)

Alcohol and bone.

It is well known that the prolonged use of excess alcohol causes a multiplicity of abnormal clinical, biochemical and electrophysiological changes that are associated with diseases of the liver, neuromuscular system, heart and brain. It is less well appreciated that the long-term use of excess alcohol also effect bone and may play an important role in the causation of extensive bone loss, and osteoporosis.