Can transcription factors in the intervertebral disc of lopinavir/ritonavir prevent degeneration in the nucleus pulposus by mediating the regulation of inflammation through signaling pathways?

OBJECTIVE: This study was conducted to examine whether lopinavir/ritonavir (Lop/r), an HIV protease inhibitor, can improve disc physiology and slow down intervertebral disc (IVD) degeneration through in vitro experimental methods, as well as whether it can suppress inflammation with interleukin-1 beta (IL-1ß) and sex-determining region Y (SRY) protein-related high-mobility group box genes-9 (SOX9) through hypoxia-inducible factor 1-alpha (HIF-1α) and the nuclear factor kappa B (NF-κB) signaling pathway. The aim was to investigate whether Lop/r application is toxic to IVD cells and the microenvironment simultaneously. PATIENTS AND METHODS: Human primary cell cultures were prepared using herniated IVD tissues obtained from patients with lumbar disc hernia who were unresponsive to conservative and medical treatment, and thereby, were operated on. The untreated culture samples served as control group, and the samples treated with Lop/r served as study group. Microscopic evaluations were performed simultaneously using fluorescent and supravital dyes in all groups. In addition to cell viability, toxicity, and proliferation analysis through a commercial kit, IL-1ß, SOX9, HIF-1α, and NF-κB protein expressions were evaluated using Western blotting. In the statistical comparison of the obtained data, an alpha value less than 0.05 was considered significant. RESULTS: Cell proliferation decreased in the Lop/r group, but no cell death was observed (p < 0.05). Moreover, at the end of 72 hours after Lop/r application, IL-1ß and NF-kB protein expressions decreased by 40% and 52%, respectively, while HIF-1α and SOX9 protein expressions increased by 4% and 59%, respectively (p< 0.05). CONCLUSIONS: Although these data were obtained from an in vitro experimental study, it is believed that these findings could make significant contributions to the pharmaco-regenerative treatment modalities of IVD degeneration. Lop/r suppresses the IL-1ß and NF-κB and induces SOX9 and HIF-1α, since these signaling pathways may be related to human IVD degeneration.

Does oseltamivir protect human chondrocyte and nucleus pulposus cells from degeneration by inhibiting senescence and proinflammation mediated by the NLRP3 inflammasome and NF-κB?

OBJECTIVE: Recent drug design studies suggest that inflammation is among the most important factors in the development of both intervertebral disc (IVD) degeneration (IVDD) and osteoarthritis (OA) due to cartilage damage. This study aimed to investigate whether the anti-inflammatory drug oseltamivir has a toxic effect on IVD and cartilage tissue cells. It assessed what effect oseltamivir has on hypoxia-inducible factor (HIF)-1 alpha (HIF1α), which plays an important role in anabolic pathways in IVD and cartilage tissue. In addition, the study analyzed whether oseltamivir could inhibit the release of inflammatory interleukin-1 beta (IL-1ß) via the nuclear factor kappa-B (NF-κB) signaling pathway by activating the nucleotide-binding oligomerization domain and leucine-rich repeat protein-3 (NLRP3) inflammasome. MATERIALS AND METHODS: Human lumbar IVD (n = 8) tissues were isolated for annulus fibrosus (AF) and nucleus pulposus (NP) primary cell cultures, and human tibial and femoral cartilage tissues (n = 8) were isolated for primary chondrocyte cultures. Untreated groups served as the control and oseltamivir-treated groups as the study sample. Cell viability and cytotoxicity were evaluated at 0, 24, 48, and 72 h in all groups for changes in HIF-1α, IL-1ß, NF-κB, and the NLRP3-inflammasome protein expressions using Western blotting. The α significance value was < 0.05. RESULTS: In the oseltamivir-treated groups, cell proliferation decreased in both AF/NP cell and chondrocyte cultures obtained from IVD cartilage tissues. After Western blotting analysis, changes were observed in the protein expressions of HIF-1α, IL-1ß, NF-κB, and the NLRP3 inflammasome in both AF/NP cells and chondrocytes. The results were statistically significant (p < 0.05). CONCLUSIONS: Oseltamivir treatment may be a promising regenerative strategy to manage IVDD and osteoarthritic cartilage tissues.

Effects of an acetylcholinesterase inhibitor and an N-methyl-D-aspartate receptor antagonist on inflammation and degeneration of the nucleus pulposus.

OBJECTIVE: The study aimed to examine the effects of two drugs, an acetylcholinesterase inhibitor (AChEI) and an N-methyl-D-aspartate receptor (NMDAR) antagonist, on degenerated annulus fibrosus (AF) and nucleus pulposus (NP) cells and the extracellular matrix (ECM) structure in vitro. PATIENTS AND METHODS: Tissue samples were obtained from patients with intervertebral disc herniation (four males and four females; classified as Pfirmann stage IV) and used to prepare cell cultures. Untreated cell culture samples served as the control group. Study group samples were treated with donepezil, memantine or a combination of the two drugs. Cell viability, toxicity and proliferation were evaluated in all groups. Western blotting was used to examine changes in protein expression of signal transducer and activator of transcription 3 (STAT3), phospho-STAT3 (ser727), hypoxia-inducible factor (HIF)-1 alpha (HIF-1α) and nucleotide-binding oligomerisation domain (NOD) leucine-rich repeat (LRR)-containing proteins (NLR) family pyrin domain containing 3 (NLRP3) inflammasome. The alpha significance value was < 0.05. RESULTS: Analysis of the microscopy and commercial kit results revealed that cell proliferation was suppressed, and no cell death was observed. The protein expression levels of NLRP3, STAT3, ser727 and HIF-1α were lower in the samples treated with donepezil and memantine at 72 h (p < 0.05). The protein expression levels of NLRP3, STAT3, ser727 and HIF-1α were higher in the samples treated with the combination of donepezil and memantine (p < 0.05). CONCLUSIONS: The combined administration of memantine a NMDAR antagonist which can prevent neurodegeneration and donepezil an AChEI used for pain relief increased the protein expression levels in the anabolic pathway. However, it did not reduce the protein expression levels in the catabolic pathway. Therefore, further studies are needed to provide extensive insight into whether it may be among the potential targets for the therapy of intervertebral disc (IVD) diseases.

Pharmaco-molecular assessment of the effects of anandamide and its antagonists on hippocampal tissue in Wistar albino rats.

OBJECTIVE: The members of the matrix metalloproteinase (MMP) family and cannabinoids (CBs) are reportedly associated with hippocampus-dependent memory functions. However, the effects of endogenously formed CBs on hippocampal long-term potentiation remain unknown. The present study aimed to investigate the changes in the gene and protein expression levels of matrix metallopeptidase 9 (MMP-9), phosphatase and tensin homolog (PTEN), and NOTCH receptor 1 (NOTCH1) in rat hippocampal tissues treated with anandamide (AEA), AM251, 6-iodopravadolin (AM630), and N-[4-{[(3,4-Dimethyl-5-isoxazolyl)amino]sulfonyl}phenyl] (ML193). MATERIALS AND METHODS: The subjects were divided into 10 groups (n = five per group). The pharmaceuticals were administered via intraperitoneal injection once a day for seven days, except for the control group. The resected hippocampal tissues were then evaluated using a quantitative real-time polymerase chain reaction (RT-qPCR) and Western blot analysis. The data obtained were statistically analyzed, and p < 0.01 was considered statistically significant. RESULTS: Contrary to the literature, the changes in MMP-9 expression were not statistically significant, but the changes in PTEN and NOTCH1 were. The findings of this in vivo experimental study revealed that the agonists and antagonists acting on the CB system have significant molecular effects on hippocampal tissue. CONCLUSIONS: The changes in gene and protein expressions may be one of the reasons for the neurodegenerative processes observed in patients using these agonists and antagonists, whose effects on the CB system have not been fully explained yet. Our study can contribute to the literature as it is the first study investigating the MMP-9, PTEN and NOTCH1 gene and protein expression.

Convincing evidence for the Halperin-Lubensky-Ma effect at the N-SmA transition in alkyloxycyanobiphenyl binary mixtures via a high-resolution birefringence study.

We present new high-resolution experimental data for the temperature behavior of optical birefringence for a series of mixture of the liquid crystals octyloxycyanobiphenyl (8OCB) and nonyloxycyanobiphenyl (9OCB) by using a rotating analyzer technique. The birefringence data have been used to probe the temperature dependence of the nematic order parameter [Formula: see text]. We have then arrived at values for possible entropy discontinuities at the nematic-smectic A transition temperature [Formula: see text] from the detailed inspection of [Formula: see text] data in the immediate vicinity of [Formula: see text]. The 9OCB mole fraction dependence of the obtained reduced entropy discontinuities has been shown to be well fitted with a crossover function which is itself consistent with the mean-field free energy expression with a non-zero cubic term arising from the Halperin-Lubensky-Ma (HLM) coupling. The obtained results are in good accordance with existing results from adiabatic scanning calorimetry (ASC). Our birefringence results and determined entropy discontinuities (consistent with calorimetry results) are in striking contrast with the recent birefringence results of Barman et al. (Phase Transit. 91, 58 (2018) published online 16 Aug. 2017) claiming second-order nematic-to-smectic A transitions for all mixtures. In this paper we present a possible explanation for this discrepancy. We have also extracted the effective critical exponent values [Formula: see text] characterizing the critical fluctuations near the N-SmA transition for all compositions by using the fact that the temperature derivative of the order parameter [Formula: see text] near [Formula: see text] exhibits the same power-law divergence as the specific heat capacity. Measurable latent heat values were extracted from optical birefringence data for mole fractions of 9OCB where the [Formula: see text] values are as low as 0.2, which is substantially lower than the tricritical value [Formula: see text]. This is qualitatively different from what has been observed so far in other liquid-crystal systems. Together with ASC data, these pecuilarities of the 8OCB+9OCB system render further convincing evidence for the presence of the HLM coupling effect at the N-SmA transition phase transition line.

Effects of Foeniculum vulgare essential oil compounds, fenchone and limonene, on experimental wound healing.

We investigated the wound healing efficacy of the Foeniculum vulgare compounds, fenchone and limonene, using an excisional cutaneous wound model in rats. An excision wound was made on the back of the rat and fenchone and limonene were applied topically to the wounds once daily, separately or together, for 10 days. Tissue sections from the wounds were evaluated for histopathology. The healing potential was assessed by comparison to an untreated control group and an olive oil treated sham group. We scored wound healing based on epidermal regeneration, granulation tissue thickness and angiogenesis. After day 6, wound contraction with limonene was significantly better than for the control group. Ten days after treatment, a significant increase was observed in wound contraction and re-epithelialization in both fenchone and limonene oil treated groups compared to the sham group. Groups treated with fenchone and with fenchone + limonene scored significantly higher than the control group, but the difference was not statistically significant compared to the olive oil treated group. Our findings support the beneficial effects of fenchone and limonene for augmenting wound healing. The anti-inflammatory and antimicrobial activities of fenchone and limonene oil increased collagen synthesis and decreased the number of inflammatory cells during wound healing and may be useful for treating skin wounds.

Bioassay-guided isolation of the antinociceptive compounds motiol and beta-sitosterol from Scorzonera latifolia root extract.

Scorzonera latifolia (Asteraceae) is a plant widely distributed in Central and East Anatolia. A mastic, named yaki sakizi, is prepared from the latex and roots of S. latifolia and similar species. This latex is used in Turkish folk medicine for its analgesic activity, as anthelmintic and against infertility. The aim of this study was to isolate the compounds responsible for the antinociceptive activity of S. latifolia using bioassay-guided fractionation. The methanolic extract of the S. latifolia roots was prepared and subjected to chromatographic purification. Isolated active compounds were identified by means of MS and NMR techniques. Writhing and tail-flick tests were used to determine antinociceptive activity. Motiol and beta-sitosterol were isolated as compounds with promising antinociceptive activity. It is suggested that antinociceptive activity of the plant extract is probably caused by the synergic interaction of the isolated compounds.

High-resolution birefringence investigation of octylcyanobiphenyl (8CB): an upper bound on the discontinuity at the smectic-A to nematic phase transition.

We report optical birefringence data by two different methods with high temperature resolution for octylcyanobiphenyl (8CB) near the smectic-A to nematic (Sm-A-N) phase transition temperature T(AN). Within the resolution of our experiments, we find that the Sm-A-N phase transition is continuous. For a possible discontinuity in the orientational order parameter S(T) at T(AN), we arrive at an upper limit of 0.0002, which is substantially smaller than other estimates in literature, but consistent with the value of 0.00008 derived from the upper limit of the latent heat from high-resolution adiabatic scanning calorimetry (ASC), which is itself consistent with the Halperin-Lubensky-Ma theory. The temperature derivative of the order parameter exhibits a power law divergence with a critical exponent that is consistent with the value α = 0.31 ± 0.03 for the specific heat capacity obtained by ASC.

Evaluation of analgesic, anti-inflammatory and hepatoprotective effects of lycorine from Sternbergia fisheriana (Herbert) Rupr.

The present study reports the potential antinociceptive, anti-inflammatory and hepatoprotective activities of lycorine from Sternbergia fischeriana (Herbert) Rupr. (Amaryllidaceae). Lycorine was evaluated on mice by using acetic-acid induced writhing and tail-flick tests. Lycorine exhibited stronger inhibition than aspirin in acetic-acid induced abdominal stretching at 1.0mg/kg dose. Lycorine also showed antinociceptive activity at 1.0mg/kg dose in tail-flick test. The anti-inflammatory activity of lycorine was not found to be significant at dose of 0.5mg/kg. However, at doses of 1.0mg/kg and 1.5mg/kg, i.p. showed a significant reduction with 53.45% and 36.42%, respectively in rat paw oedema induced by carrageenan against the reference anti-inflammatory drug indomethacin (3mg/kg, i.p.) (95.70%). The ED(50) of lycorine was determined as 0.514 mg/kg. Hepatoprotective activity of lycorine on carbon tetrachloride (CCl(4)) induced acute liver toxicity following biochemical parameters were also evaluated. Rats were treated with lycorine at doses of 1.0mg/kg and 2.0mg/kg, i.p. Results of biochemical tests were confirmed by histopathological examination. Lycorine exhibited significant hepatoprotective effect at dose of 2.0mg/kg i.p. dose.

First Report of Group 16SrXII Phytoplasma Causing Stolbur Disease in Potato Plants in the Eastern and Southern Anatolia Regions of Turkey.

In recent years, a stolbur-like disease has had devastating effects on the yield and marketable quality of potato production in Erzurum (Eastern Anatolia) and Akcakale-Sanliurfa (Southern Anatolia) regions of Turkey. Potato plants exhibited several different symptoms including stunting, upward rolling of the top leaves along with reddish or purplish coloration, chlorosis, shortened internodes, swollen nodes, proliferated axillary buds, aerial tubers, and early plant decline. An extensive survey from 2003 to 2010 was performed and diseased plant samples were collected. Total genomic DNAs were isolated from the leaf mid-veins of the six different symptomatic and two symptomless plants selected. Nested-PCRs, carried out by using phytoplasma-universal primer pair P1/P7 followed by R16F2n/R16R2 (2), amplified 16S rDNA fragments (F2nR2) from only templates derived from symptomatic plants. F2nR2 PCR products from two independent symptomatic plants were cloned and sequenced from both directions with M13 universal primers. The obtained 16S rDNA sequence (GenBank Accession No HM485579) was subjected to virtual restriction fragment length polymorphism (RFLP) analysis using iphyclassifier software (3). Results indicated that the phytoplasma, here identified in association with potato plants, shared best sequence identity (99%) with members of subgroup 16SrXII-A (e.g., GenBank Accession No. EU010006). Moreover, collective RFLP pattern of potato-associated phytoplasma differed from digestion profiles of previously described 16SrXII subgroups, sharing best similarity coefficient (0.94) with the reference phytoplasma strain of subgroup 16SrXII-A (GenBank Accession No. AJ964960). Thus, it was confirmed that potato-associated phytoplasma represents a new 16SrXII subgroup (16SrXII-N). Furthermore, a new primer set (PatsecF/PatsecR) was designed for priming specific PCR-amplification of potato-associated phytoplasma 16S rDNA sequence. PCR reaction was successfully used for specifically detecting stolbur phytoplasma in infected potato plants. The use of this method may help to determine possible alternative hosts and vectors of potato phytoplasma, which is important for development of an integrated management strategy for effective control of this disease in the future. Presence of potato stolbur diseases in the Eastern Anatolia Region of Turkey has previously been reported (1). To our knowledge, this is the first report of occurrence of a 16SrXII group phytoplasma causing potato stolbur diseases caused in the Eastern and Southern Anatolia regions of Turkey. References: (1) A. Citir. J. Turk. Phytopathol. 14:53, 1985. (2) D. E. Gundersen and I. M. Lee. Phytopathol. Mediterr. 35:144, 1996. (3)Y. Zhao et al. Int. J. Syst. Evol. Microbiol. 59:2582, 2009.

Comparison of caudal ketamine with lidocaine or tramadol administration for postoperative analgesia of hypospadias surgery in children.

BACKGROUND: This study was designed to investigate whether the addition of tramadol or lidocaine to ketamine would enhance the quality of intra- and postoperative analgesia for hypospadias surgery in children. METHODS: Sixty-two ASA PS I or II children, between 1 and 10 years of age, scheduled for hypospadias surgery were recruited. Anesthesia was induced with 6-8% sevoflurane and maintained with 0.5-2.5% sevoflurane-50% N2O in oxygen. Children were allocated randomly to receive one of two study drugs. Children in group KL received caudal ketamine (0.25 mg.kg(-1)) plus lidocaine (2%, 2 mg.kg(-1)) and in group KT ketamine (0.25 mg.kg(-1)) plus tramadol (1 mg.kg(-1)). Systemic blood pressure, heart rate, peripheral O2 saturation, sedation, and pain scores (CHEOPS) were recorded at 1, 5, 10, 15, 30, 45 min and 1, 2, 3 h following recovery from anesthesia. RESULTS: Duration of analgesia was similar in the two groups (P > 0.05). CHEOPS in group KL was lower than in group KT during the study period, except at first 15 min. Sedation scores were higher in group KL than group KT in the first 10 min (P < 0.05). Incidence of postoperative nausea and vomiting was similar in the two groups (P > 0.05) Sevoflurane concentration required was significantly lower in group KL than group KT peroperatively (P < 0.001). CONCLUSIONS: Caudal ketamine (0.25 mg.kg(-1)), plus lidocaine (2% 2 mg.kg(-1)) significantly reduced sevoflurane concentration compared with ketamine (0.25 mg.kg(-1)) + tramadol (1 mg.kg(-1)). We suggested that both ketamine + lidocaine and ketamine + tramadol provided very effective and long duration of analgesia, similarly. However, analgesia quality is superior in the ketamine-lidocaine group postoperatively.

Anti-inflammatory effects of tretinoin (all-trans-retinoic acid) 0.1% and adapalene 0.1% in rats.

In this study, the anti-inflammatory effects of tretinoin (all-trans-retinoic acid) 0.1% cream and adapalene 0.1% gel were compared in rats to determine whether there was a difference between these agents. Thirty-six rats of either sex were divided into six groups (two control groups, and an etodolac, indomethacin, tretinoin and adapalene group) of six animals each. Each group was given different drugs or chemicals. The inhibitory activities of the drugs were determined on carrageenan-induced rat-paw oedema. The inhibition rate (53.48%) in the tretinoin group was found to be higher than adapalene and controls (P < 0.05). Adapalene was found to have an inhibition rate of 10.28%, and when compared with the other groups, was found to have no statistically significant anti-inflammatory activity. We conclude that tretinoin has a higher anti-inflammatory activity than adapalene and thus should be preferred for the treatment of inflammatory lesions.

Effects of cholesterol supplementation on antioxidant enzyme activities in rat hepatic tissues: possible implications of hepatic paraoxonase in atherogenesis.

BACKGROUND AND AIM: The effects of cholesterol supplementation on antioxidant enzyme activities were investigated hepatic tissue taken from Sprague Dawley rats. METHODS AND REULTS: The study involved 14 male Sprague Dawley rats: seven fed a normal laboratory diet and seven a normal diet plus cholesterol (3.6 g/kg/day) for three months, during which blood samples were obtained to measure serum cholesterol levels. At the end of the 3-month period, the livers were surgically removed in order to measure antioxidant enzyme activities (superoxide dismutase, catalase, glutathione peroxidase and paraoxonase-1). At the end of the study period, serum total cholesterol and HDL-cholesterol levels were significantly higher in the cholesterol-fed group than the control group. There were no significant between-group differences in hepatic superoxide dismutase, catalase and glutathione peroxidase activities, but there was a significant decrease in hepatic paraoxonase-1 activity in the cholesterol-fed group. CONCLUSIONS: Cholesterol supplementation significantly decreases paraoxonase-1 activity in rat liver tissue without changing the activities of other antioxidant enzymes. These results suggest that cholesterol significantly suppresses hepatic paraoxonase-1 synthesis. It seems that the decreased paraoxinase-1 activity in the plasma HDL-fraction of atherosclerotic patients is associated with suppressed liver synthesis. A reduction in paraoxonase-1 activity may therefore lead to the more intensive exposure of LDL to oxidant attacks.

Serum levels of leptin and proinflammatory cytokines in patients with gastrointestinal cancer.

The aim was to investigate the serum levels of leptin, TNF-alpha, IL-1 beta, IL-6, insulin, and growth hormone in patients with upper gastrointestinal cancer and cachexia. A total of 39 patients with various advanced stage (stage IV) gastrointestinal malignancies were enrolled. These cancer patients were divided into two groups according to the presence or absence of cachexia. Fifteen healthy adults were recruited as the control group. Body mass index (BMI; kg/m2) was calculated. Serum leptin, tumour necrosis factor (TNF)-alpha interleukin (IL)-1 beta, interleukin (IL)-6, growth hormone, insulin, glucose, triglyceride, total protein, albumin, erythrocyte sedimentation rate, and CRP were measured. In both cancer groups (cachectic and non-cachectic) body mass index and serum leptin levels were lower than controls (p < 0.001). Serum IL-1 beta, IL-6, and growth hormone levels were higher in both cachectic and non-cachectic groups than those of controls (p < 0.05). Serum TNF-alpha level in non-cachectic group was also significantly higher than in control group (p < 0.01). There is no significant difference between three groups in terms of insulin resistance as assessed by HOMA index. Our results showed that some proinflammatory cytokine levels were increased and leptin level was decreased due to upper gastrointestinal cancers. Increased cytokine levels may lead to decreased food intake and caused a weight loss.

Effects of Nigella sativa L. and Urtica dioica L. on lipid peroxidation, antioxidant enzyme systems and some liver enzymes in CCl4-treated rats.

This study was designed to investigate the effects Nigella sativa L. (NS) and Urtica dioica L. (UD) on lipid peroxidation, antioxidant enzyme systems and some liver enzymes in carbon tetrachloride (CCl4)-treated rats. A total of 60 healthy male Sprague-Dawley rats were utilized in this study. The rats were randomly allotted into one of four experimental groups: A (CCl4-only treated), B (CCl4 + UD treated), C (CCl4 + NS treated) and D (CCl4 + UD + NS treated), each containing 15 animals. All groups received CCl4 [0.8 ml/kg of body weight, subcutaneously, twice a week for 90 days starting day 1]. In addition, B, C and D groups also received daily intraperitoneal injections of 0.2 ml/kg NS or/and 2 ml/kg UD oils for 45 days starting day 46. Group A, on the other hand, received only 2 ml/kg normal saline solution for 45 days starting day 46. Blood samples for the biochemical analysis were taken by cardiac puncture from five randomly chosen rats in each treatment group at beginning, at 45th and at 90th day of the experiment. The CCl4 treatment for 45 days increased the lipid peroxidation and liver enzymes, and also decreased the antioxidant enzyme levels. NS or UD treatments (alone or combination) for 45 days starting day 46 decreased the elevated lipid peroxidation and liver enzyme levels and also increased the reduced antioxidant enzyme levels. Live weights of the rats decreased in group A, and increased in groups B, C and D. It is concluded that NS and UD decrease the lipid peroxidation and liver enzymes, and increase the antioxidant defence system activity in the CCl4-treated rats.

The role of Urtica dioica and Nigella sativa in the prevention of carbon tetrachloride-induced hepatotoxicity in rats.

The role of Nigella sativa L. (Ranunculaceae) (NS) and Urtica dioica L. was investigated (UD) in the prevention of carbon tetrachloride (CCl4) induced liver fibrosis and cirrhosis. Fifty Sprague-Dawley rats were allocated into fi ve groups (I, IIA and B, IIIA and B) and CCl4 was injected biweekly to all groups. Group I (control, CCl4 only), group IIA and B (NS fixed oil and volatile oil), group IIIA and B (UD fixed oil and UD decoction extract) rats were killed at the end of week 12 and histopathological and immunohistochemical examinations of liver tissues were performed. In the control group, coagulation necrosis and hydropic degeneration were marked in the periacinar regions (zone 3) associated with fibrosis in the periacinar regions and in the portal tracts. In groups IIA-B and IIIA-B (NS and UD), none of the serious histopathological findings were detected except for sparse coagulation necrosis in the periacinar regions. ASMA-positive perisinusoidal cells with myo fibroblastic transformation and lysosomal enzyme activity suggesting fibrogenesis were also significantly more common in the control group than in the NS and UD groups. UD and NS seem to be significantly effective in the prevention of carbon tetrachloride induced hepatotoxicity in rats.

Utility of color duplex sonography in the assessment of efficacy of the stellate ganglion blockade.

PURPOSE: To assess the hemodynamic changes in the upper extremity arteries after sympathetic ganglion blockade (SGB) by using spectral Doppler parameters and to determine the applicability of these parameters for the evaluation of SGB efficacy. MATERIAL AND METHODS: Spectral Doppler parameters (peak systolic velocity (PSV), end diastolic velocity (EDV), mean velocity (mean V), flow volume, resistive and pulsatility indices (RI, PI), inner arterial diameters (intima to intima) (D) with simultaneous recordings of heart rate (HR), systolic and diastolic blood pressures and upper extremity surface temperature changes) were recorded before and 5 min after during the first, fifth and tenth SGB procedures. RESULTS: SGB induced an increase in skin temperature in the ipsilateral hand and persistent dilatation of the radial diameter accompanied by reduction of RI and PI in the radial and third digital arteries in all patients. CONCLUSION: Hemodynamic changes assessed by spectral Doppler parameters could be used as sensitive and objective measurements of peripheral sympathetic nervous activity and vascular tonus, and may confirm a successfully performed SGB.

Hepatoprotective effect of Foeniculum vulgare essential oil.

Hepatoprotective activity of Foeniculum vulgare (fennel) essential oil (FEO) was studied using carbon tetrachloride (CCl(4)) induced liver injury model in rats. The hepatotoxicity produced by acute CCl(4) administration was found to be inhibited by FEO with evidence of decreased levels of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and bilirubin. The results of this study indicate that FEO has a potent hepatoprotective action against CCl(4)-induced hepatic damage in rats.

Effects of sildenafil citrate, acetylcholine, and sodium nitroprusside on the relaxation of rabbit cavernosal tissue in vitro.

OBJECTIVES: To investigate the effect of sildenafil together with the influence of sodium nitroprusside and acetylcholine and further discuss its mechanism of action in vitro. METHODS: Isolated strips of rabbit corpus cavernosum were stimulated isometrically with phenylephrine. Graded relaxations were induced using increasing concentrations of acetylcholine, sodium nitroprusside, and sildenafil alone and in combination. RESULTS: The agents all relaxed the rabbit corpus cavernosal strips in a dose-dependent manner. The inhibitory potentials of the test agents were ranked (from least inhibitory to most inhibitory) as follows: sildenafil, acetylcholine plus sildenafil, sodium nitroprusside, sodium nitroprusside plus sildenafil, acetylcholine. The presence of sodium nitroprusside in the medium reduced the median effective dose for the sildenafil-induced relaxation of the cavernosal tissue from 3.65 x 10(-5) M to 2.73 x 10(-7) M, and the presence of acetylcholine reduced it to 9.79 x 10(-6) M. CONCLUSIONS: Sildenafil enhances the relaxing effect of both sodium nitroprusside and acetylcholine on the phenylephrine-induced contraction of rabbit cavernosal tissue.

Comparison of caudal morphine and tramadol for postoperative pain control in children undergoing inguinal herniorrhaphy.

OBJECTIVES: We compared the quality and duration of analgesia, the effect on perioperative sevoflurane requirement after a single, presurgical caudal block with either tramadol or morphine in children undergoing inguinal herniorrhaphy. Our study was also designed to evaluate the preemptive analgesic efficacy of morphine administered caudally in children. METHODS: Patients were randomly divided into three groups to receive 2 mg.kg-1 tramadol (group T, preemptive group) or morphine sulphate 0.03 mg.kg-1 (group M, preemptive group). The patients in control group (group C, postincisional group) received morphine sulphate 0.03 mg.kg-1 at the end of surgery, caudally. Cardiorespiratory data, sedation and pain were recorded for 24 h following recovery from anaesthesia. RESULTS: There were no differences between the three groups in baseline blood pressure or heart rate; or duration of anaesthesia, surgery. The inhaled sevoflurane concentration was significantly lower in group M and group T than in the control group. The quality and duration of postoperative pain relief did not differ between the three groups. There were no intergroup differences in postoperative nausea, vomiting, or other complications. CONCLUSION: Caudal tramadol (2 mg.kg-1) provided reliable postoperative analgesia similar to caudal morphine (0.03 mg.kg-1) in quality and duration of pain relief in our study children who were undergoing herniorrhaphy. We also concluded that presurgical caudal morphine or tramadol reduced perioperative sevoflurane requirements and either presurgical or postsurgical caudal morphine did not make any difference to postoperative analgesia.