Essential oil of Zygophyllum album inhibits key-digestive enzymes related to diabetes and hypertension and attenuates symptoms of diarrhea in alloxan-induced diabetic rats

Context: Zygophyllum album L. (Zygophyllaceae), commonly known as Bougriba, is widely used to treat diabetes, digestive tract spasm, and hypertension in folk medicine, in Tunisia.

Objective: This study investigates the antidiabetic, antidiarrheal, and antihypertensive activities of the leaves of the essential oil from Zygophyllum album (OZA) in alloxan-induced diabetic rats.

Materials and methods: The oil was obtained by hydrodistillation and analyzed by GC-MS. Males rats were divided into four groups: control, diabetic-untreated group, diabetic-treated group with acarbose (10?mg/kg), and diabetic-treated rats with OZA (200?mg/kg) for 30 d.

Results: At the end of the experimental period, the OZA significantly decreased the activity of α-amylase in pancreas and serum of the diabetic rats by 43% and 38%, respectively, which led to reduce the serum glucose level by 60% and lower of glycated hemoglobin (HbA1c) rate by 17% as compared with untreated diabetic animals. Moreover, the OZA treatment attenuated symptoms of diarrhea, improved lipid disorders, and hypertension through inhibiting the pancreatic lipase and angiotensin-converting enzyme (ACE) activities by 47% and 25%, respectively, in serum of diabetic rats.

Conclusion: OZA showed a good effect in the management of diabetes mellitus and exerted preventive action from related hypertension.     

Anomalies in bulk supercooled water at negative pressure

Water anomalies still defy explanation. In the supercooled liquid, many quantities, for example heat capacity and isothermal compressibility κ_T, show a large increase. The question arises if these quantities diverge, or if they go through a maximum. The answer is key to our understanding of water anomalies. However, it has remained elusive in experiments because crystallization always occurred before any extremum is reached. Here we report measurements of the sound velocity of water in a scarcely explored region of the phase diagram, where water is both supercooled and at negative pressure. We find several anomalies: maxima in the adiabatic compressibility and nonmonotonic density dependence of the sound velocity, in contrast with a standard extrapolation of the equation of state. This is reminiscent of the behavior of supercritical fluids. To support this interpretation, we have performed simulations with the 2005 revision of the transferable interaction potential with four points. Simulations and experiments are in near-quantitative agreement, suggesting the existence of a line of maxima in κ_T (LMκ_T). This LMκ_T could either be the thermodynamic consequence of the line of density maxima of water [Sastry S, Debenedetti PG, Sciortino F, Stanley HE (1996) Phys Rev E 53:6144–6154], or emanate from a critical point terminating a liquid–liquid transition [Sciortino F, Poole PH, Essmann U, Stanley HE (1997) Phys Rev E 55:727–737]. At positive pressure, the LMκ_T has escaped observation because it lies in the “no man’s land” beyond the homogeneous crystallization line. We propose that the LMκ_T emerges from the no man’s land at negative pressure.Water differs in many ways from standard liquids: ice floats on water, and, upon cooling below 4°C, the liquid density decreases. In the supercooled liquid, many quantities, for example heat capacity and isothermal compressibility, show a large increase. Extrapolation of experimental data suggested a power-law divergence of these quantities at ?45°C (1). Thirty years ago, the stability-limit conjecture proposed that an instability of the liquid would cause the divergence (2) (Fig. 1A). This is supported by equations of state (EoSs), such as the International Association for the Properties of Water and Steam (IAPWS) EoS (3), fitted on the stable liquid and extrapolated to the metastable regions. Ten years later, the second critical point interpretation, based on simulations (4), proposed that, instead of diverging, the anomalous quantities would reach a peak, near a Widom line (5, 6) that emanates from a liquid–liquid critical point (LLCP) terminating a first-order liquid–liquid transition (LLT) between two distinct liquid phases at low temperature (Fig. 1B). The two scenarios differ in the shape of the line of density maxima (LDM) of water (Fig. 1 A and B). A recent work (7) has added one point on this line at large negative pressure, but this was not enough to decide between the two scenarios.Open in a separate windowFig. 1.Scenarios proposed to explain water anomalies. Schematic phase diagrams for water in the pressure–temperature plane with equilibrium transitions between liquid, vapor, and ice (solid blue curves); T is the triple point and C the liquid–vapor critical point. (A) Stability-limit conjecture (2). If the LDM (long-dashed purple curve) reaches the liquid–vapor (LV) spinodal (dashed-dotted red curve) at negative pressure, the latter bends to lower tension at lower temperature. This would provide a line of instability at positive pressure on which several thermodynamic functions would diverge. (B) Second critical-point scenario (4). The LDM bends to lower temperatures at larger tension, and the LV spinodal remains monotonic. The anomalies of supercooled water are due to the vicinity of an LLCP terminating an LLT (solid orange curve). Thermodynamic functions exhibit a peak on lines emanating from the LLCP (5, 6), such as the line of isothermal compressibility maxima along isobars (LMκ_T, short-dashed green curve). (C) Critical-point free scenario (9–11). The LLT extends down to the LV spinodal, so that there is no accessible LLCP. The spinodal associated with the LLT (LL spinodal, dashed-dotted orange curve) would cause the divergence of several thermodynamic functions. (D) Singularity-free interpretation (12). There is no LLT or LLCP. Thermodynamic functions do not diverge, but several exhibit extrema as a consequence of the existence of an LDM. The LDM reaches its highest temperature when it crosses one of the lines of isothermal compressibility extrema along isobars; the case where it is the line of minima (Lmκ_T, dotted green curve) is displayed.It has been argued (8) that the stability-limit conjecture would imply the existence of an improbable second, low-temperature liquid–vapor critical point. However, it is not necessary if the line of instability at positive pressure is not a liquid–vapor spinodal, but rather a line of instability toward another phase. The critical-point free scenario (9–11) (Fig. 1C) provides such a line. There would be an LLT, but its critical point would be absent because it lies beyond the liquid–vapor spinodal. The low-density liquid could become metastable at low temperature, but unstable on the liquid–liquid spinodal, where κ_T would diverge. Finally, the singularity-free scenario (12) (Fig. 1D) does not exhibit any LLT. It predicts peaks in several thermodynamic quantities instead of divergences, which would be “the thermodynamically inevitable consequences of the existence of density anomalies” (8). It may also be seen as a second critical-point interpretation, but with an LLCP at zero temperature (11, 13).In bulk water at positive pressure, despite tremendous efforts (8) decisive experiments to discriminate between the proposed scenarios have been precluded by unavoidable crystallization. To circumvent this problem, water proxies have been used: water confined in narrow pores (14), or bulk water–glycerol mixtures (15). Although the results supported the second critical-point interpretation, their relevance to bulk water is not straightforward.Here we study bulk water samples, a few micrometers in diameter, in the doubly metastable region: the liquid is simultaneously supercooled and exposed to mechanical tension or negative pressure. Negative pressures occur in nature, e.g., in the sap of trees, under the tentacles of octopi, or in fluid inclusions in minerals (16, 17). The study of the largest tensions achievable in water was pioneered by the group of Angell (18). They used a “Berthelot tube” technique (Fig. 2A), based on isochoric cooling of a micrometer-size inclusion of water in quartz. Tensions as large as ?140?MPa have been reported, and confirmed by others (7, 19, 20), which exceed by far the limit of other techniques (16, 17). It was already recognized in the work of Angell that the high-density water inclusions that were able to survive cooling to room temperature without cavitation were also able to be supercooled below 0°C. Indeed, when the isochore crosses the LDM of water, the tension is released and cavitation becomes less likely. Another study (21) using macroscopic Berthelot tubes also reached the doubly metastable region, but the tensions were around ?10?MPa only.Open in a separate windowFig. 2.Experiments on metastable liquid water. (A) Berthelot tube method (7, 18–20). A closed, rigid container with a fixed amount of water is heated until the last vapor bubble disappears at T_h. Upon cooling, the bubble does not reappear and the liquid follows an isochore (green curve) and is put under mechanical tension. If the density is high enough, cavitation does not occur and the liquid can reach the doubly metastable region, where water is both supercooled and under tension. (B) Typical Brillouin spectra. They were obtained with the homogenized sample 1 at 140°C (red circles) and ?12°C (blue diamonds). The solid curves are fits used to obtain the sound velocity (Materials and Methods, Brillouin Light Scattering). Note that the ?12°C spectrum was rescaled to the same exposure time as the 140°C spectrum for easier comparison. The samples are shown as inset (scale bars, 10?μm).To reach large tensions, we use two microscopic inclusions of water in quartz (Fig. 2B, Inset) (Materials and Methods, Samples). We perform Brillouin light-scattering experiments on these samples; this technique gives access to the sound velocity within the liquid. Several Brillouin light-scattering studies on supercooled water at ambient pressure are available (22–27), but only two works investigated water under tension. One used fluid inclusions (19): all samples in that study cavitated above room temperature except one with a density close to that of our sample 1. However, measurements in ref. 19 were reported only down to 0°C, and the direct comparison with an extrapolated EoS was not considered. Another work (28) confirmed the validity of the extrapolation of the IAPWS EoS, but only at room temperature and down to −26 MPa. Our work extends the covered range to supercooled water under tension, reporting measurements down to ?15°C along two isochores at ρ₁ = 933.2 ± 0.4?kg?m^?3 and ρ₂ = 952.5 ± 1.5?kg?m^?3, and reaching pressures beyond ?100?MPa (SI Text).     

Determination of Synthetic Musks in Surface Sediment from the Bizerte Lagoon by QuEChERS Extraction Followed by GC-MS

A new analytical method for the simultaneous determination of eight synthetic musks compounds (SMs) including five polycyclic musks (PCMs) and three nitro musks (NMs) was validated for sediment samples based on a simple QuEChERS (Quick, Easy, Cheap, Effective, Rugged and Safe) sample preparation procedure followed by gas chromatography–mass spectrometry (GC–MS). Good analytical performances were obtained for all the target compounds. For the validation of the method, internal calibration (IC) and internal calibration with QuEChERS (ICQ) were compared. Good linearity was obtained for both calibration methods with determination coefficients (R²) ranging between 0.990 for Musk Xylene (MX) and 0.999 for Tonalide (AHTN) with IC and between 0.991 for Musk Ketone (MK) and 0.999 for Traseolide (ATII) with ICQ. The repeatability ranges were 0.1?%–1.9?% with the IC and 0.1?%–2.6?% with the ICQ. The apparent recoveries obtained for SMs in the standard reference sediment (SRM1944) varied in the range of 70?%–98?% and 75?%–103?% in the sediment from the Bizerte Lagoon (Tunisia). The absolute recoveries ranged between 61?% and 92?% for the SRM1944 and between 61?% and 89?% in the sediment from the Bizerte Lagoon. The limits of detection (LOD) calculated for the two main compounds, Galaxolide (HHCB) and Tonalide (AHTN) were 0.3 and 0.1 ng g^?1 respectively. The LODs obtained for ADBI (Celestolide), AHMI (Phantolide), ATII (Traseolide), MM (Muks mosken), MK (Musk Ketone) and MX (Musk Xylene) were 0.08, 0.12, 0.03, 0.34, 0.11, 0.08, 0.10 and 0.15 ng g^?1 respectively. The levels of ∑SMs in surface sediments from the Bizerte Lagoon ranged from 1.4 to 4.5 ng g^?1, which are 1000 times lower that the predicted no effect concentration (PNEC) for marine organisms.     

A Tunisian Case of Oculo-dento-digital Syndrome Revealed by Spastic Paraplegia

Oculo-dento-digital syndrome (ODD) is a rare congenital disorder that associates eye and facial abnormalities, defects in teeth enamel and type III syndactyly. It is a genetic disorder inherited in an autosomal dominant fashion and displays high penetrance but variable clinical expression. A few patients with ODD syndrome also manifest spastic paraparesis. The authors report a sporadic case with ODD syndrome, who was referred for evaluation of spastic paraplegia associated with bladder dysfunction. The report shows that ODD syndrome can be recognized in late adulthood and revealed by spastic paraplegia. Cerebral MRI must be carried out to complete the phenotyping of this syndrome.     

Cytotoxic effects exerted by polyarylsulfone dialyser membranes depend on different sterilization processes

Polyarylsulfone group is one of the most important polymeric materials used in the biomedical field, due to its excellent properties, such as good thermal, chemical, and mechanical stability. There are three important polyarylsulfone polymers, all of which have excellent electrical properties: polysulfone (PSu), polyarylsulfone (PAS) and polyarylethersulfone (PAES). All these polymers have excellent creep, radiation and high temperature resistance. In this study, we aimed to determine the effect of three sterilization processes (steam, ethylene oxide and gamma rays) on cytotoxicity of polyarylsulfone dialysis membranes. Ten long-term dialysis patients and ten age-matched healthy controls were enrolled in our study. We analysed (1) serum effect on cultured endothelial cell viability using MTT assay and (2) lipid peroxidation assessed by serum malondialdehyde (MDA) formation at the beginning (T0), the middle (T2) and the end (T4) of haemodialysis (HD) session. Our results clearly showed that steam-sterilized membranes improve endothelial cell viability when compared to ethylene oxide or gamma rays-sterilized ones. Moreover, there is a increased generation of MDA in patients sera during HD session. The serum MDA concentration was about 3, 6 and 10 times higher, respectively, for steam, ethylene oxide and gamma rays sterilization procedures when compared to the MDA amount in healthy subject sera. We concluded that using steam instead of ethylene oxide or gamma rays for sterilization may improve the biocompatibility of polyarylsulfone membranes.     

Neoadjuvant or adjuvant chemotherapy: what is the best treatment of muscle invasive bladder cancer?

Bladder cancer is the fourth most common cancer for men and the eighth most common cancer for women. Transitional cell carcinoma is the most predominant histological type. Bladder cancer is highly chemosensitive. In metastatic setting the treatment is based on cisplatin chemotherapy regimens type MVAC, MVAC-HD or gemcitabine plus cisplatin. The standard treatment of muscle invasive operable bladder cancer (T2–T4) used widely was radical cystectomy with pelvic lymph nodes dissection; the anatomical extent of pelvic lymphadenectomy has not accurately been defined so far. However, in the last decade, the treatment of tumors was improved by the introduction of chemotherapy as part of the management of the disease. Neoadjuvant chemotherapy should be considered at first, as standard treatment of choice, before local treatment for patients with good performance status (0–1) and good renal function–glomerular filtration rate (GFR) >60 mL/min. For patients treated with primary surgery, adjuvant chemotherapy is a valuable option in the case of lymph nodes involvement. This brief review would provide the evidence of the role of neoadjuvant chemotherapy in the management of operable muscle invasive (T2–T4) bladder cancer.     

Modulation of trichloroethylene in vitro metabolism by different drugs in rats

Trichloroethylene (TCE) is a widely used chemical to which humans are frequently exposed. Toxicological interactions with drugs are among factors having the potential to modulate the toxicity of TCE. The aim of this study was to identify metabolic interactions between TCE and 14 widely used drugs in rat suspended hepatocytes and characterize the strongest using microsomal assays (oxidation and/or glucuronidation). The concentrations of TCE and its metabolites, trichloroethanol (TCOH) and trichloroacetate (TCA), were measured by gas chromatography with injection headspace coupled to mass spectrometry (GC–MS). Results in hepatocyte incubations show that selected drugs can be segregated into four groups: group 1: drugs causing no significant interactions (five drugs: amoxicillin, carbamazepine, ibuprofen, mefenamic acid and ranitidine); group 2: increasing both TCE metabolites (two drugs: naproxen and salicylic acid); group 3: decreasing both TCE metabolites (five drugs: acetaminophen, gliclazide, valproic acid, cimetidine and diclofenac) and group 4: affecting only one (two drugs: erythromycin and sulphasalazine). Naproxen and salicylic acid (group 2) and acetaminophen, gliclazide and valproic acid (from group 3) presented the strongest interactions (i.e. drugs changing metabolite levels by 50% or more). For group 2 drugs, characterization in rat microsomes confirmed interaction with naproxen only, which was found to partially competitively inhibit TCOH glucuronidation (K_i = 211.6 μM). For group 3 selected drugs, confirmation was positive only for gliclazide (K_i = 58 μM for TCOH formation) and valproic acid (K_i = 1215.8 μM for TCA formation and K_i = 932.8 μM for TCOH formation). The inhibition was found to be partial non competitive for both drugs. Our results confirm the existence of interactions between TCE and a variety of widely used drugs. Further efforts are undertaken to determine if these interactions are plausible in humans and if they can impact the risk of toxicity of TCE in medicated population.     

Effect of aerobic training on insulin resistance and C-reactive protein (CRP) levels and subcutaneous abdominal in obese women

This study examined the effect of three training intensities on abdominal obesity, insulin resistance, and C-reactive protein (CRP) levels. Forty-three young obese women (age 20–30 years; body mass index 30–40 kg/m²) underwent 12 weeks of walking programs (i.e., 5 days/week). They were randomly assigned to one of four groups: low-intensity training group [G1, 50 % of heart rate reserve (HRR), n = 11], high-intensity training group (G2, 75 % of HRR, n = 10), alternated-intensity training group (G3, 50–75 % of HRR, n = 12), and control group (G0, n = 10). They were tested before (T0) and after (T1) 12 weeks of aerobic training to determine changes in body mass, body mass index (BMI), total fat, waist circumference (WC), leptin, HOMA-IR, glucose and CRP. Body mass, BMI, total fat, and WC were significantly lower at T1 than T0 (p < 0.001) in all training groups. However, the decrease was higher in G2 than G1 and G3. Leptin levels decreased significantly in G1, G2, and G3 (p < 0.05). Only G1 showed significant decreases in CRP levels (p < 0.05). Insulin, HOMA-IR, and glucose levels decreased in the three training groups with higher decrease in G1. The low-intensity training is more effective than the high-intensity training or alternated-intensity training for improving insulin sensitivity and reducing subclinical inflammation.