Role of cyclooxygenases 1 and 2 in the maintenance of colonic mucosal integrity in an experimental colitis model.

The role of cyclooxygenase (COXs) isoforms in maintaining colonic mucosal integrity is not fully understood. This study aimed to evaluate the role of COX-1 and -2 on colonic mucosal integrity in an experimental colitis model. Colitis was induced in Wistar rats by intracolonic administration of 2,4,6-trinitrobenzenesulfonic acid (20 mg + 50% ethanol). The control group (sham group) received saline only. After 7, 14, or 28 days, colonic samples were removed, and macroscopic lesion scores, wet weight, myeloperoxidase activity, and transepithelial electrical resistance (TER) were determined. In other rat groups, colonic samples from the sham group and a 7th day post-colitis group were mounted in Üssing chambers with the luminal side exposed to a buffer solution (control), acetylsalicylic acid (ASA), SC-560 (COX-1 inhibitor), or celecoxib (COX-2 inhibitor). TER and epithelial permeability to fluorescein were measured. The 7th day colitis group had higher macroscopic damage scores, wet weight, and myeloperoxidase activity and lower basal TER than the sham, 14th day colitis, and 28th day colitis groups. Inhibition of COX-1 but not COX-2 significantly decreased TER and increased permeability to fluorescein in the 7th day post-colitis group compared to the sham group. Additionally, ASA decreased the colonic mucosal integrity on day seven post-colitis compared to the sham group. A decrease in the colonic mucosa integrity in the experimental colitis model can be aggravated only by the inhibition of COX-1, which demonstrated the importance of this enzyme in the maintenance of colonic mucosal integrity.

The compound event that triggered the destructive fires of October 2017 in Portugal.

Portugal is regularly affected by destructive wildfires that have severe social, economic, and ecological impacts. The total burnt area in 2017 (∼540,000 ha) marked the all-time record value since 1980 with a tragic toll of 114 fatalities that occurred in June and October events. The local insurance sector declared it was the costliest natural disaster in Portugal with payouts exceeding USD295 million. Here, the 2017 October event, responsible for more than 200,000 ha of burnt area and 50 fatalities is analyzed from a compound perspective. A prolonged drought led to preconditioned cumulative hydric stress of vegetation in October 2017. In addition, on 15 October 2017, two other major drivers played a critical role: 1) the passage of hurricane Ophelia off the Coast of Portugal, responsible for exceptional meteorological conditions and 2) the human agent, responsible for an extremely elevated number of negligent ignitions. This disastrous combination of natural and anthropogenic drivers led to the uncontrolled wildfires observed on 15 October.

Role of cyclooxygenases 1 and 2 in the maintenance of colonic mucosal integrity in an experimental colitis model

The role of cyclooxygenase (COXs) isoforms in maintaining colonic mucosal integrity is not fully understood. This study aimed to evaluate the role of COX-1 and -2 on colonic mucosal integrity in an experimental colitis model. Colitis was induced in Wistar rats by intracolonic administration of 2,4,6-trinitrobenzenesulfonic acid (20 mg + 50% ethanol). The control group (sham group) received saline only. After 7, 14, or 28 days, colonic samples were removed, and macroscopic lesion scores, wet weight, myeloperoxidase activity, and transepithelial electrical resistance (TER) were determined. In other rat groups, colonic samples from the sham group and a 7th day post-colitis group were mounted in Üssing chambers with the luminal side exposed to a buffer solution (control), acetylsalicylic acid (ASA), SC-560 (COX-1 inhibitor), or celecoxib (COX-2 inhibitor). TER and epithelial permeability to fluorescein were measured. The 7th day colitis group had higher macroscopic damage scores, wet weight, and myeloperoxidase activity and lower basal TER than the sham, 14th day colitis, and 28th day colitis groups. Inhibition of COX-1 but not COX-2 significantly decreased TER and increased permeability to fluorescein in the 7th day post-colitis group compared to the sham group. Additionally, ASA decreased the colonic mucosal integrity on day seven post-colitis compared to the sham group. A decrease in the colonic mucosa integrity in the experimental colitis model can be aggravated only by the inhibition of COX-1, which demonstrated the importance of this enzyme in the maintenance of colonic mucosal integrity.

Evaluation of miRNAs regulation of BDNF and IGF1 genes in T2DM insulin resistance in experimental models: bioinformatics based approach.

microRNAs (miRNAs) are recognized as diabetes mellitus type 2 (T2DM) biomarkers useful for disease metabolism comprehension and have great potential as therapeutics targets. BDNF and IGF1 increased expression are highly involved in the benefits of insulin and glucose paths, however, they are down-regulated in insulin resistance conditions, while their expression increase is correlated to the improvement of glucose and insulin metabolism. Studies suggest the microRNA regulation of these genes in several different contexts, providing a novel investigation approach for comprehending T2DM metabolism and revealing potential therapeutic targets. In the present study, we investigate in different animal models (human, rat, and mouse) miRNAs that target BDNF and IGF1 in skeletal muscle tissue with T2DM physiological conditions. Bioinformatics tools and databases were used to miRNA prediction, molecular homology, experimental validation of interactions, expression in the studied physiological condition, and network interaction. The findings showed three miRNAs candidates for IGF1(miR-29a, miR-29b, and miR-29c) and one for BDNF (miR-206). The experimental evaluations and the search for the expression in skeletal muscle from T2DM subjects confirmed the predicted interaction between miRNA-mRNA for miR-29b and miR-206 through human, rat, and mouse models. This interaction was reaffirmed in multiple network analyses. In conclusion, our results show the regulation relationship between miR-29b and miR-206 with the investigated genes, in several tissues, suggesting an inhibition pattern. Nevertheless, these data show a large number of possible interaction physiological processes, for future biotechnological prospects.

Role of TRPV1 receptor in inflammation and impairment of esophageal mucosal integrity in a murine model of nonerosive reflux disease.

BACKGROUND: Microscopic inflammation and impairment of the esophageal epithelial barrier are considered relevant for perception of symptoms in patients with nonerosive reflux disease (NERD). In these patients, the receptor transient receptor potential vanilloid 1 (TRPV1) is overexpressed in the esophageal mucosa, but its role is not yet fully understood. We evaluated the role of TRPV1 in esophageal inflammation and mucosal barrier impairment in a murine model of NERD. METHODS: Nonerosive reflux disease was surgically induced in Swiss mice by pyloric substenosis and ligature of the gastric fundus, and the mice were killed 7 days post surgery. The experimental groups were: I, sham surgery (negative control); II, NERD untreated; III and IV, NERD + SB366791 or capsazepine (TRPV1 antagonists); and V, NERD + resiniferatoxin (for long-term desensitization of TRPV1). The esophagus was collected for western blotting and histopathology and for evaluation of wet weight, myeloperoxidase (MPO), keratinocyte-derived chemokine (KC), transepithelial electrical resistance (TEER), and basal permeability to fluorescein. KEY RESULTS: Compared to sham, NERD mice had increased esophageal wet weight and MPO and KC levels. The mucosa had no ulcers but exhibited inflammation. NERD mice showed mucosal TRPV1 overexpression, a more pronounced decrease in TEER at pH 0.5 (containing pepsin and taurodeoxycholic acid), and increased basal permeability. Pharmacological modulation of TRPV1 prevented esophageal inflammation development, TEER changes by acidic exposure, and increase in esophageal permeability. CONCLUSIONS & INFERENCES: The TRPV1 receptor has a critical role in esophageal inflammation and mucosal barrier impairment in NERD mice, suggesting that TRPV1 might be a pharmacological target in patients with NERD.

Sensory and inflammatory colonic changes induced by vincristine in distinct rat models of colitis.

Preclinical and clinical studies show that gastrointestinal (GI) inflammation can evoke sensory changes occasionally far from the original inflammatory site. Animal models of colitis with either trinitrobenzenesulphonic acid (TNBS) or mustard oil (MO) produce distinct patterns of somatic and visceral sensory changes. We evaluated the effects of four doses of i.v. vincristine 150 µg kg(-1) (total of 600 µg kg(-1) ) treatment on the somatic (thermal nociceptive threshold) and colonic (morphological) changes induced by TNBS or MO in rats. TNBS and MO groups were further submitted to vincristine or saline pretreatments. TNBS induced somatic hypersensitivity, while MO induced somatic hyposensitivity (P < 0.05) when compared to the saline and ethanol control groups. Vincristine per se induced somatic hypersensitivity (P < 0.05). This effect was enhanced by TNBS and reversed by MO treatments. Although vincristine increased the colitis area (colonic weight length(-1) ratio) and the Morris' score in TNBS-treated rats, it did not alter the colitis area and even lowered the Morris' score in MO-treated rats. Compared to the saline (control) group, vincristine did not alter the colonic microscopic pattern. However, such lesions scores are higher (P < 0.05) in colitis groups induced by TNBS and MO, pretreated or not with vincristine. In conclusion, the somatic changes induced by different models of experimental colitis are diverse and modulated differently by vincristine.

Oxidative stress in acute pancreatitis: lost in translation?

Oxidative stress has been implicated in the pathogenesis of acute pancreatitis, a severe and debilitating inflammation of the pancreas that carries a significant mortality, and which imposes a considerable financial burden on the health system due to patient care. Although extensive efforts have been directed towards the elucidation of critical underlying mechanisms and the identification of novel therapeutic targets, the disease remains without a specific therapy. In experimental animal models of acute pancreatitis, increased oxidative stress and decreased antioxidant defences have been observed, changes also detected in patients clinically. However, despite the promise of studies evaluating the effects of antioxidants in these model systems, translation to the clinic has thus far been disappointing. This may reflect many factors involved in the design of both preclinical and clinical evaluations of antioxidant therapy, not least the fact that most experimental studies have focussed on pre-treatment rather than post-injury assessment. This review has examined evidence relating to the involvement of oxidative stress in the pathophysiology of acute pancreatitis, focussing on experimental models and the clinical experience, including the experimental techniques employed and potential of antioxidant therapy.

The hydrogen sulfide donor, Lawesson's reagent, prevents alendronate-induced gastric damage in rats.

Our objective was to investigate the protective effect of Lawesson's reagent, an H2S donor, against alendronate (ALD)-induced gastric damage in rats. Rats were pretreated with saline or Lawesson's reagent (3, 9, or 27 µmol/kg, po) once daily for 4 days. After 30 min, gastric damage was induced by ALD (30 mg/kg) administration by gavage. On the last day of treatment, the animals were killed 4 h after ALD administration. Gastric lesions were measured using a computer planimetry program, and gastric corpus pieces were assayed for malondialdehyde (MDA), glutathione (GSH), proinflammatory cytokines [tumor necrosis factor (TNF)-α and interleukin (IL)-1ß], and myeloperoxidase (MPO). Other groups were pretreated with glibenclamide (5 mg/kg, ip) or with glibenclamide (5 mg/kg, ip)+diazoxide (3 mg/kg, ip). After 1 h, 27 µmol/kg Lawesson's reagent was administered. After 30 min, 30 mg/kg ALD was administered. ALD caused gastric damage (63.35 ± 9.8 mm(2)); increased levels of TNF-α, IL-1ß, and MDA (2311 ± 302.3 pg/mL, 901.9 ± 106.2 pg/mL, 121.1 ± 4.3 nmol/g, respectively); increased MPO activity (26.1 ± 3.8 U/mg); and reduced GSH levels (180.3 ± 21.9 µg/g). ALD also increased cystathionine-γ-lyase immunoreactivity in the gastric mucosa. Pretreatment with Lawesson's reagent (27 µmol/kg) attenuated ALD-mediated gastric damage (15.77 ± 5.3 mm(2)); reduced TNF-α, IL-1ß, and MDA formation (1502 ± 150.2 pg/mL, 632.3 ± 43.4 pg/mL, 78.4 ± 7.6 nmol/g, respectively); lowered MPO activity (11.7 ± 2.8 U/mg); and increased the level of GSH in the gastric tissue (397.9 ± 40.2 µg/g). Glibenclamide alone reversed the gastric protective effect of Lawesson's reagent. However, glibenclamide plus diazoxide did not alter the effects of Lawesson's reagent. Our results suggest that Lawesson's reagent plays a protective role against ALD-induced gastric damage through mechanisms that depend at least in part on activation of ATP-sensitive potassium (KATP) channels.

The hydrogen sulfide donor, Lawesson's reagent, prevents alendronate-induced gastric damage in rats

Our objective was to investigate the protective effect of Lawesson's reagent, an H2S donor, against alendronate (ALD)-induced gastric damage in rats. Rats were pretreated with saline or Lawesson's reagent (3, 9, or 27 µmol/kg, po) once daily for 4 days. After 30 min, gastric damage was induced by ALD (30 mg/kg) administration by gavage. On the last day of treatment, the animals were killed 4 h after ALD administration. Gastric lesions were measured using a computer planimetry program, and gastric corpus pieces were assayed for malondialdehyde (MDA), glutathione (GSH), proinflammatory cytokines [tumor necrosis factor (TNF)-α and interleukin (IL)-1β], and myeloperoxidase (MPO). Other groups were pretreated with glibenclamide (5 mg/kg, ip) or with glibenclamide (5 mg/kg, ip)+diazoxide (3 mg/kg, ip). After 1 h, 27 µmol/kg Lawesson's reagent was administered. After 30 min, 30 mg/kg ALD was administered. ALD caused gastric damage (63.35±9.8 mm2); increased levels of TNF-α, IL-1β, and MDA (2311±302.3 pg/mL, 901.9±106.2 pg/mL, 121.1±4.3 nmol/g, respectively); increased MPO activity (26.1±3.8 U/mg); and reduced GSH levels (180.3±21.9 µg/g). ALD also increased cystathionine-γ-lyase immunoreactivity in the gastric mucosa. Pretreatment with Lawesson's reagent (27 µmol/kg) attenuated ALD-mediated gastric damage (15.77±5.3 mm2); reduced TNF-α, IL-1β, and MDA formation (1502±150.2 pg/mL, 632.3±43.4 pg/mL, 78.4±7.6 nmol/g, respectively); lowered MPO activity (11.7±2.8 U/mg); and increased the level of GSH in the gastric tissue (397.9±40.2 µg/g). Glibenclamide alone reversed the gastric protective effect of Lawesson's reagent. However, glibenclamide plus diazoxide did not alter the effects of Lawesson's reagent. Our results suggest that Lawesson's reagent plays a protective role against ALD-induced gastric damage through mechanisms that depend at least in part on activation of ATP-sensitive potassium (KATP) channels.

Gastroprotective activity of Zanthoxylum rhoifolium Lam. in animal models.

ETHNOPHARMACOLOGICAL RELEVANCE: The stem barks of Zanthoxylum rhoifolium Lam. (Rutaceae), locally known as "mamica de cadela", are popularly used in dyspepsies, stomachic, tonic, antitumoral, antipyretic and are used in treating flatulence and colic. The objective of this study was to evaluate the gastroprotective effect of the ethanolic extract of Zanthoxylum rhoifolium (EEZR) stem barks in acute gastric lesion models, investigating their possible mechanisms. MATERIALS AND METHODS: Mice were used for the evaluation of the acute toxicity, and mice and rats to study the gastroprotective activity. The gastroprotective action of EEZR was analyzed in the absolute ethanol, HCl/ethanol and indomethacin-induced gastric lesion models in mice, hypothermic-restraint stress, and ischemia/reperfusion in rats. In the investigation of the gastroprotective mechanisms of EEZR, the participation of the NO-synthase pathway, ATP-sensitive potassium channels (K(ATP)), the levels of the non-protein sulfhydril groups (NP-SH) and the catalase activity using the ethanol-induced gastric mucosa lesion model and the quantification of the gastric mucus and the antisecretory activity through pylorus ligature model in rats were analyzed. RESULTS: The animals did not present any signs of acute toxicity for the EEZR (up to the 4 g/kg dose, po), and it was not possible to calculate the DL(50). EEZR (125-500 mg/kg) exhibited a significant gastroprotective effect in absolute ethanol, HCl/ethanol, hypothermic-restraint stress, and ischemia/reperfusion-induced gastric lesion models. EEZR (250 and 500 mg/kg) exhibited still a gastroprotective activity in the indomethacin-induced ulcer model. Gastroprotection of EEZR was significantly decreased in pre-treated mice with l-NAME or glibenclamide, the respective nitric oxide synthase and K(ATP) channels inhibitors. Our studies revealed that EEZR (500 mg/kg) prevented the decrease of the non-protein sulfhydril groups (NP-SH) and increased the catalase levels in ethanol-treated animals. Furthermore, the extract (500 mg/kg) significantly increased the mucus production, however, the gastric secretion parameters (volume, [H(+)], pH) did not show any alteration. CONCLUSIONS: Our results indicate that the ethanolic extract of Zanthoxylum rhoifolium exhibits a significant gastroprotection, because it inhibits the formation of gastric lesions using different models. The release of the nitric oxide, the opening of the K(ATP) channels, the participation of the non-protein sulfhydril groups (NP-SH), catalase and the increase of mucous secretion seem to be involved in the gastroprotection activity of the EEZR. Nevertheless, this activity does not seem to be related to antisecretory mechanisms.

Testicular Sertoli cell function in male systemic lupus erythematosus.

OBJECTIVE: To assess the testicular Sertoli cell function in male SLE patients. METHODS: Thirty-four consecutive patients were prospectively selected to evaluate serum inhibin B. Clinical features, treatment, semen analysis, urological evaluation, testicular ultrasound, hormones and anti-sperm antibodies were determined. RESULTS: Patients were subdivided into two groups: low serum inhibin B (Group 1, n = 8) and normal levels (Group 2, n = 26). The median sperm concentration (P = 0.024), total sperm count (P = 0.023) and total motile sperm count (P = 0.025) were lower in Group 1. Inhibin B levels were positively correlated with sperm concentration (r = 0.343), total motile sperm count (r = 0.357), and negatively correlated with follicule-stimulating hormone (FSH) (r = 0.699) and luteinizing hormone (r = 0.397). The median serum inhibin B was lower in SLE patients treated with intravenous cyclophosphamide (IVCYC) compared with those without this therapy (P = 0.031). Further evaluation of the 26 SLE patients with normal inhibin B and FSH levels revealed that medians of inhibin B/FSH ratio were lower in SLE patients with oligozoospermia compared with normozoospermia (P = 0.004). This ratio was also lower in SLE patients treated with IVCYC than those without this therapy (P = 0.04). In contrast, inhibin B serum level alone did not discriminate the later group of patients (P = 0.12). CONCLUSIONS: This is the first study to identify a high frequency of testicular Sertoli cell dysfunction in male SLE associated with semen abnormalities. Further prospective studies are necessary to determine if inhibin levels and inhibin B/FSH ratio will be an earlier and useful marker of IVCYC toxicity in these patients.

Role of the NO/cGMP/K(ATP) pathway in the protective effects of sildenafil against ethanol-induced gastric damage in rats.

BACKGROUND AND PURPOSE: Sildenafil is a selective inhibitor of cGMP-specific phosphodiesterase. Sildenafil, acting via NO-dependent mechanisms, prevents indomethacin-induced gastropathy. Activation of ATP-sensitive potassium channels (K(ATP)) is involved in gastric defence. Our objective was to evaluate the role of the NO/cGMP/K(ATP) pathway in the protective effects of sildenafil against ethanol-induced gastric damage. EXPERIMENTAL APPROACH: Rats were treated with L-NAME (1 or 3 mg kg(-1), i.p.) or with L-arginine (200 mg kg(-1), i.p.) + L-NAME (3 mg kg(-1), i.p.), the guanylate cyclase inhibitor, ODQ (10 mg kg(-1), i.p.), glibenclamide (0.1, 0.3, 1 or 3 mg kg(-1), i.p.) or with glibenclamide (1 mg kg(-1), i.p.) + diazoxide (3 mg kg(-1), i.p.). After thirty minutes, the rats received sildenafil (1 mg kg(-1), by gavage), followed by intragastric instillation of absolute ethanol (4 ml kg(-1)) to induce gastric damage. One hour later, gastric damage (haemorrhagic or ulcerative lesions) was measured with a planimetry programme. Samples of stomach were also taken for histopathological assessment and for assays of tissue glutathione and haemoglobin. KEY RESULTS: Sildenafil significantly reduced ethanol-induced gastric damage in rats. L-NAME alone, without L-arginine, significantly reversed the protection afforded by sildenafil. Inhibition of guanylate cyclase by ODQ completely abolished the gastric protective effect of sildenafil against ethanol-induced gastric damage. Glibenclamide alone reversed sildenafil's gastric protective effect. However, glibenclamide plus diazoxide did not alter the effects of sildenafil. CONCLUSIONS: Sildenafil had a protective effect against ethanol-induced gastric damage through the activation of the NO/cGMP/K(ATP) pathway.

Temporal variation of chemical composition and relaxant action of the essential oil of Ocimum gratissimum L. (Labiatae) on guinea-pig ileum.

The medicinal plant Ocimum gratissimum L. (Labiatae) is widely encountered in the Northeast of Brasil where it is used to treat digestive problems. Its leaves have an essential oil (EOOG) content whose chemical composition varies according to the time of plant collection. We have compared the effects of the EOOG, collected at 08:00 a.m. (EOOG8) and at 12:00 a.m. (EOOG12), on the relaxation of guinea-pig isolated ileum. Both EOOG8 and EOOG12 (30-300 microg/ml) reversibly relaxed the spontaneous tonus of the guinea-pig ileum in a concentration-dependent manner, with similar IC50 values (49.3 and 23.8 microg/ml, respectively). The magnitude of the decrease in resting tonus was similar to that of the recognised smooth muscle relaxant papaverine. EOOG8 and EOOG12 relaxed 60 mM KCl-precontracted preparations similarly (38.33 +/- 9.91 microg/ml and 35.53 +/- 6.70), whereas a significantly more potent relaxant effect of EOOG12 compared to EOOG8 was observed when tissues were contracted using 10 microM acetylcholine (IC50 values of 69.55 +/- 4.93 and 128.16 +/- 15.70 microg/ml, respectively; p < 0.05). The principal constituents of the essential oil, eugenol and cineole, also relaxed KCl-precontracted preparations, although they were less potent than EOOG, suggesting that they alone were not responsible for EOOG-induced relaxations. Our results show that the essential oil extracted from the leaves of O. gratissimum L., collected at different time periods, exerts significant relaxant effects on isolated guinea-pig ileum which may underlie the therapeutic action of the plant.

Inhibitory effects of the essential oil of Mentha pulegium on the isolated rat myometrium.

The effects of the essential oil of Mentha pulegium L. (EOMP), a plant commonly known as "pennyroyal" or "poejo" that is used in folk medicine as an abortifaceant, were assessed on the isolated rat myometrium. Myometrial strips were stimulated with 10 nM oxytocin or 10 microM PGF (2alpha). EOMP (10 - 300 microg/mL) concentration-dependently and reversibly inhibited the amplitude of oscillatory contractions, being approximately 3-fold more active against contractions stimulated by oxytocin than those by PGF (2alpha) (IC (50) values of 45.7 +/- 5.6 microg/mL and 160.9 +/- 5.9 microg/mL , respectively), although the maximal inhibitory effect occurred at the same concentration (300 microg/mL ) in both cases. This action was shared by pulegone (30 - 300 microM), the principal component of the essential oil (IC (50) values of 21.8 +/- 2.1 microg/mL and 12.7 +/- 4.6 microg/mL , respectively). Nifedipine (30 nM - 30 microM) also abolished agonist-stimulated contractions, and was approximately twice and 12 times as potent as EOMP in inhibiting oxytocin- and prostaglandin F (2alpha) (PGF (2alpha))-stimulated contractions, respectively. In conclusion, our results show that the essential oil of the abortifaceant plant Mentha pulegium exerts an inhibitory effect on the contractile activity of the isolated rat myometrium. This oil shares a common effect with the voltage-dependent calcium channel (VDCC) blocker nifedipine, although ostensibly acting via a different mechanism. It thus appears that EOMP and pulegone do not exert direct toxic effects on the myometrium per se that would cause abortion, and other possibilities such as systemic metabolism of plant constituents may rather underlie the abusive use of Mentha pulegium in popular medicine.

Antinociceptive properties of the essential oil of Ocimum gratissimum L. (Labiatae) in mice.

We have investigated the antinociceptive effects of the essential oil of Ocimum gratissimum L. (Labiatae) (EOOG) in two classical models of pain in male Swiss mice (25-35 g), the writhing test and the formalin test. At doses of 30, 100 and 300 mg/kg (po), EOOG produced a dose-dependent inhibition (from 58.3 4.4 to 40.7 6.3, 36.4 3.6 and 24.6 3.6, respectively; N = 8-10, P<0.05) of acetic acid-induced writhing, causing up to a ~60% inhibition at the highest dose used, comparable to that obtained with indomethacin (10 mg/kg, po). At the same doses, EOOG predominantly inhibited the late (inflammatory) phase of the formalin-induced pain response (from 59.3 8.3 to 40.4 4.8, 23.2 2.8 and 25.3 5.5, respectively; N = 6, P<0.05), with a maximal reduction of ~60% of the control, although a significant reduction of the initial (neurogenic) phase was also observed at 300 mg/kg (from 62.5 6.07 to 37 5.9; P<0.05). On the basis of these data, we conclude that EOOG possesses interesting antinociceptive properties in the writhing and formalin tests. Due to the relatively low toxicity of EOOG, further detailed examination is strongly indicated for a better characterization of its pharmacological properties and its potential therapeutic value.

Antinociceptive properties of the essential oil of Ocimum gratissimum L. (Labiatae) in mice

We have investigated the antinociceptive effects of the essential oil of Ocimum gratissimum L. (Labiatae) (EOOG) in two classical models of pain in male Swiss mice (25-35 g), the writhing test and the formalin test. At doses of 30, 100 and 300 mg/kg (po), EOOG produced a dose-dependent inhibition (from 58.3 ± 4.4 to 40.7 ± 6.3, 36.4 ± 3.6 and 24.6 ± 3.6, respectively; N = 8-10, P<0.05) of acetic acid-induced writhing, causing up to a 60 percent inhibition at the highest dose used, comparable to that obtained with indomethacin (10 mg/kg, po). At the same doses, EOOG predominantly inhibited the late (inflammatory) phase of the formalin-induced pain response (from 59.3 ± 8.3 to 40.4 ± 4.8, 23.2 ± 2.8 and 25.3 ± 5.5, respectively; N = 6, P<0.05), with a maximal reduction of 60 percent of the control, although a significant reduction of the initial (neurogenic) phase was also observed at 300 mg/kg (from 62.5 ± 6.07 to 37 ± 5.9; P<0.05). On the basis of these data, we conclude that EOOG possesses interesting antinociceptive properties in the writhing and formalin tests. Due to the relatively low toxicity of EOOG, further detailed examination is strongly indicated for a better characterization of its pharmacological properties and its potential therapeutic value

Precordial mapping in acute myocardial infarction.

Serial precordial mapping was done in 30 patients with acute anterior myocardial infarction, 27 transmural and 3 subendorcardial. The sum of ST elevations in the 48 lead map was designated as sigma ST. Normal sigma ST was calculated as 27.1+/-3.1 in males and 14.3+/-2.8 in females. In infarction it was 100.4+/-58.2 in males and 84.8+/-50.9 in females on the 1st day of admission. Sigma ST was elevated on day 1 and tended to fall gradually. In 6 patients it was normal by day 7 and in 7 it was still abnormal by day 21. This fall roughly correlated with fall in SGOT and CPK levels. Significant elevation of sigma ST occurred in 14 of 27 cases after day 1. In 10 of 27 cases significant re-elevation occurred on day 4 or after i.e. when the patient was outside the ICCU. In 10 of the 14 re-elevations there was pain or worsening of clinical picture and in 12 there was re-elevation of SGOT. This elevation presumably implied infarct extension. There was a tendency to more arrhythmias in the patients with higher sigma ST and of the 4 deaths in the series 3 had very high sigma ST and high levels of SGOT. The patient with the highest sigma ST 295 died in cardiogenic shock. The number of risk factors was found to be higher in the high sigma ST group.