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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-1a) and the nuclear factor kappa B (NF-B) 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-1a, and NF-B 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-1a 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-B and induces SOX9 and HIF-1a, since these signaling pathways may be related to human IVD degeneration. [ABSTRACT FROM AUTHOR]

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 (HIF1a), 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-1β) 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-1β, NF-κB, and the NLRP3-inflammasome protein expressions using Western blotting. The a 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-1β, 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. [ABSTRACT FROM AUTHOR]

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-1a) 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-1a 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-1a 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. [ABSTRACT FROM AUTHOR]

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 (MMP9), 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. [ABSTRACT FROM AUTHOR]

We investigated the wound healing efficacy of theFoeniculum vulgarecompounds, 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. [ABSTRACT FROM AUTHOR]

The present study investigated the analgesic and hepatoprotective activities of a water extract of Ononis spinosa L. (OS) in mice. Analgesic activity was based on the pain thresholds measured with the tail-flick test before administration at 30, 90 and 150 min. The results were analysed with one-way variance analysis. The extract of Ononis spinosa showed analgesic activity equivalent to aspirin at 30 and 90 min and even higher than aspirin with the 50 mg/kg dose. At a dose of 100 mg/kg OS showed an analgesic effect equivalent to aspirin at all time points.The hepatoprotective influence of OS on carbon tetrachloride (CCl(4))-induced acute liver toxicity was also studied. The extract had no significant effect on the increased levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and bilirubin in CCl(4) treated animals (p > 0.05). Thus, the results reveal that the extract of OS had no hepatoprotective effect on CCl(4)-induced acute liver toxicity. Copyright (c) 2006 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Summary 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. [ABSTRACT FROM AUTHOR]

Migration of roundworms into the biliary tree is a well-known complication of Ascaris lumbricoides infestation of the intestine. Massive infestation of the hepato-biliary tract is uncommon but can lead to complications if not treated. Here, we report two cases of acalculous cholecystitis caused by ascariasis. [ABSTRACT FROM AUTHOR]

Abstract.: 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 S(T). We have then arrived at values for possible entropy discontinuities at the nematic-smectic A transition temperature TNA from the detailed inspection of S(T) data in the immediate vicinity of TNA. 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 αeff characterizing the critical fluctuations near the N-SmA transition for all compositions by using the fact that the temperature derivative of the order parameter S(T) near TNA 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 αeff values are as low as 0.2, which is substantially lower than the tricritical value αTCP=0.5. 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.Graphical abstract: [ABSTRACT FROM AUTHOR]

High-resolution optical birefringence measurements are reported on the weakly first order nematic-isotropic (N–I) and the continuous nematic-smectic A (N–Sm A) phase transitions in smectic liquid crystal 8CB (octylcyanobiphenyl) doped with both pristine multi-walled carbon nanotubes (p-MWCNTs) and carboxyl group (-COOH) functionalized MWCNTs (f-MWCNTs). It has been observed that the inclusion of MWCNTs substantially decreases both the N–I and the N–Sm A transition temperatures compared to 8CB host while the order of the transitions remains the same being the I–N weakly first-order and the N-SmA continuous for all 8CB-MWCNT composites regardless of the surface functionalization. The optical birefringence data have been used to probe the temperature behavior of the nematic order parameter S (T) in the vicinity of both the N–I and the N–Sm A transitions. Sufficiently far away from the Sm A phase, the average value of the critical exponent β characterizing the limiting behavior of S (T) near the N–I transition was found to be 0.245 ± 0.002 This value of β seems to be in accord with the tricritical nature (TCH) of the N–I transition. Thus, concluded is the fact that the nature of the N–I transition of nanomaterial-based composites dispersed in liquid crystals remains tricritical up to at least the reported dopant contents and within the experimental resolution. The pre-transitional smectic behavior has also been noted to continue up to 4.3 K on average above T N A for all 8CB-MWCNT composites. From the detailed inspection of S (T) data in the immediate vicintiy of the N–Sm A transition T N A , we have then obtained the upper limits for a possible latent heat Δ H N A across T N A for all 8CB-MWCNT composites. A slight change in Δ H N A has been observed due to the inclusion of MWCNTs as compared to 8CB host. By exploiting the fact that the temperature derivative of the order parameter S (T) near T N A exhibits the same power law divergence as the specific heat capacity, we have also extracted the effective critical exponent α values characterizing the critical fluctuations near the N-SmA transition for all 8CB-MWCNT composites. From both α and Δ H N A values, we have concluded that the nematic and smectic fluctuations remain essentially bulk-like for both 8CB-p-MWCNT and 8CB-f-MWCNT composites and thus the fact that the coupling between the N and the Sm A order parameters for all composites are comparable to that of 8CB host has been documented. Image 1 • High-resolution birefringence data of 8CB-p-MWCNTs and 8CB-f-MWCNTs composites. • The pre-transitional smectic behavior up to 4:3 K for all 8CB-MWCNT composites. • The upper limits for a possible latent heat ΔHNA across TNA for all composites. • Bulk-like the nematic and smectic uctuations all 8CB-MWCNT composites. [ABSTRACT FROM AUTHOR]

Adhesion molecules are integral membrane proteins that have cytoplasmic, transmembrane and extracellular domains. Dozens of different adhesion molecules have been identified, but, adhesion molecules are conventionally divided into four main groups, each of which has a different function: 1. The selectins, 2. The immunglobulin gene superfamily, 3. The integrins and 4. The cadherins. Under normal conditions, there is little or no cell-surface expression of adhesion molecules. Various inflammatory processes induce their expressions, such as atherosclerosis and cerebral ischemia, with the upregulations mediated by cytokines. Normally, vascular endothelial cells have low adhesiveness for leukocytes; however, when stimulated they express adhesion molecules at their surfaces responsible for adhesion and activation of leukocytes as a precondition for transendothelial migration of leukocytes. The effect of anti-adhesion molecule strategies in focal cerebral and spinal cord ischemia showed a beneficial effect in models in which transient focal ischemia was followed by reperfusion, but not in models of permanent ischemia. In addition anti-inflammatory agents could have reduced expression and shedding of adhesion molecules as a result of its antiinflammatory properties. [ABSTRACT FROM AUTHOR]