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A workshop was held in Casablanca, Morocco, in March 2012, to enhance knowledge of climate extremes and their changes in the Arab region. This workshop initiated intensive data compilation activities of daily observational weather station data from the Arab region. After conducting careful control processes to ensure the quality and homogeneity of the data, climate indices for extreme temperatures and precipitation were calculated. This study examines the temporal changes in climate extremes in the Arab region with regard to long-term trends and natural variability related to ENSO and NAO. We find consistent warming trends since the middle of the 20th Century across the region. This is evident in the increased frequencies of warm days and warm nights, higher extreme temperature values, fewer cold days and cold nights and shorter cold spell durations. The warming trends seem to be particularly strong since the early 1970s. Changes in precipitation are generally less consistent and characterised by a higher spatial and temporal variability; the trends are generally less significant. However, in the western part of the Arab region, there is a tendency towards wetter conditions. In contrast, in the eastern part, there are more drying trends, although, these are of low significance. We also find some relationships between climate extremes in the Arab region and certain prominent modes of variability, in particular El Niño-Southern Oscillation ( ENSO) and North Atlantic Oscillation ( NAO). The relationships of the climate extremes with NAO are stronger, in general, than those with ENSO, and are particularly strong in the western part of the Arab region (closer to the Atlantic Ocean). The relationships with ENSO are found to be more significant towards the eastern part of the area of study. © 2013 Royal Meteorological Society [ABSTRACT FROM AUTHOR]

The article discusses the report regarding weather and climatic changes across the world. It says that the global climate observing system (GCOS) has identified essential climate variables (ECVs) that are valuable to support the United Nations Framework Convention on Climate Change and the Intergovernmental Panel on Climate Change. It suggests that observations and adjustments are needed for effective monitoring of historical data in order to remove artificial biases.

An abstract regarding the weather and climate events across the world is presented.

The 2,4,6-trinitrobenzene sulfonic acid (TNBS) -induced model of chronic inflammation of the rat colon was used to determine the efficacy of bismuth subsalicylate (BSS), bismuth subcitrate (CBS), and 5-aminosalicylic acid (5-ASA) administered in enema form. A novel bismuth compound 1, 2-bis[2-(1,3-dithiobismolane)thio]ethane [Bi2(EDT)3] was also tested. On day 1 colitis was induced with 50 mg TNBS/50% ethanol in female Sprague-Dawley rats, while controls received a saline enema. On day 3, twice-daily treatment with enemas of either saline, BSS, CBS, Bi2(EDT)3, or 5-ASA were initiated in the colitis and control rats. All rats were killed on day 14, and the colons excised, weighed, rated macroscopically, and then fixed for hematoxylin and eosin staining. Blinded microscopic scoring was used to determine injury and healing in all groups. Colon mass and macroscopic scores were increased (P < 0.05) in the group of rats treated with TNBS (N = 16) compared to saline controls (N = 12). Colon mass and macroscopic scores in controls treated with BSS (N = 4), CBS (N = 4), Bi2(EDT)3 (N = 4), and 5-ASA (N = 4) alone did not differ from saline control animals. Macroscopic scoring showed a decrease (P < 0.05) in the degree of damage in the group of rats treated with TNBS plus BSS (N = 15), TNBS plus Bi2(EDT)3 (N = 10) and TNBS plus CBS (N = 4) compared to the group of rats treated with TNBS plus saline (N = 16). A decrease (P < 0.05) in injury and an increase (P < 0.05, Kruskal-Wallis) in healing was observed in the groups of rats treated with TNBS plus BSS, TNBS plus CBS, and TNBS plus 5-ASA compared to the group of rats treated with TNBS plus saline. It appeared that Bi2(EDT)3 was not protective against injury at the microscopic level but that the novel Bi2(EDT)3 has an effective healing capacity at the macroscopic level. We conclude that BSS and CBS decrease injury and/or promote healing as effectively as 5-ASA in this model.

This study assessed the ability of ursodeoxycholic acid (UDCA) and one of its metabolites, tauroursodeoxycholic acid (TUDCA), to inhibit platelet derived growth factor (PDGF) stimulated fibroproliferation and compared these results to the effect of pentoxifylline and its metabolite-1 [1-(5-hydroxyhexyl)-3,7-dimethylxanthine] and assessed the potential role of cyclic AMP in this process. Fibroproliferative activity was measured by the tritiated thymidine uptake assay in human fibroblast cultures. All four compounds: pentoxifylline, metabolite-1, UDCA and TUDCA inhibited the fibroproliferative activity stimulated by PDGF (8 ng/ml). Incubation of fibroblasts with dibutyryl cyclic AMP reduced proliferation stimulated by PDGF suggesting that the PDGF stimulated proliferation was sensitive to inhibition by a membrane permeable analogue of cyclic AMP. Incubation of myofibroblasts with dibutyryl cyclic AMP significantly inhibited PDGF stimulated proliferation suggesting that cyclic AMP can regulate PDGF stimulated proliferation in the myofibroblast. To determine if the effect of pentoxifylline on fibroproliferation was mediated by cyclic AMP, we used dideoxyadenosine, a potent inhibitor of adenylyl cyclase. The effect of pentoxifylline on fibroproliferation was not prevented by dideoxyadenosine, which inhibits formation of cyclic AMP, thus suggesting that the inhibitory effect of pentoxifylline on PDGF-stimulated proliferation of fibroblasts was not mediated by cyclic AMP, arguing against a role for cyclic AMP in this process. Combinations of UDCA (250 microM) plus pentoxifylline (120 microM) or UDCA (250 microM) plus TUDCA (250 microM) inhibited fibroproliferative activity stimulated by PDGF to a greater extent than either drug alone. As UDCA has been reported to decrease cyclic AMP these results argue against a role for cyclic AMP in this process. Finally the results suggest that UDCA may inhibit PDGF-stimulated proliferation via an inhibition of C-kinase.

Fibroblast proliferation and extracellular matrix accumulation are two major events occurring in fibrosis. Hepatic stellate cells are the major collagen-producing cells of the liver and are transformed into proliferative myofibroblasts following activation. Whether proliferation and extracellular matrix production are regulated by the same cytokines is not known. Monocyte-conditioned medium obtained from pigs with yellow phosphorus-induced hepatic fibrosis increased the collagen production by cultured procine myofibroblasts. Liver biopsies from these same fibrotic animals had increased levels of collagen alpha 1(I) and alpha 1(III) mRNA compared to control animals. Preincubation with platelet-derived growth factor (PDGF) B/B antibody significantly reduced the collagen-stimulating ability of the monocyte-conditioned medium. Recombinant PDGF stimulated proliferation in nonconfluent myofibroblasts and stimulated collagen production in confluent cultures of myofibroblasts without increasing cell number, suggesting that these events can occur independent of each other. Pentoxifylline and one of its active metabolites (metabolite-1) inhibited PDGF-stimulated collagen production in cultured porcine myofibroblasts. These results demonstrate the importance of PDGF in the pathogenesis of liver fibrosis and provide evidence that pentoxifylline interferes with PDGF-mediated events during experimental liver fibrosis.

Objectives: To evaluate drug treatment of functional dyspepsia (including Helicobacter pylori) and provide guidelines for future trials based on a critical systematic overview of published studies., Methods: Data sources were a Medline search for articles published in English going back to 1966 and a manual search of four GI journals going back to 1980. Original randomized, double-blind, placebo-controlled trials were selected that enrolled at least 20 patients. Using a standardized, pretested data extraction form, studies were evaluated independently by two observers for study design, outcome measures, and results., Results: Fifty two eligible studies were evaluated. Many studies suffered from important weaknesses in study design and execution. Only five studies used previously validated outcome measures., Conclusions: Because of suboptimal design and/or unclear presentation of the data, none of the trials provided unequivocal evidence that there is efficacious therapy for the treatment of functional dyspepsia.

Fibroproliferation was studied in two animal models of liver disease. Oral feeding of yellow phosphorus to pigs reproducibly results in fibrosis after 8 weeks of feeding, extensive fibrosis after 12 weeks and cirrhosis after 16 weeks of yellow phosphorus. Bile duct ligation was used to induce cirrhosis in the rat. Fibroproliferation was assessed as uptake of tritiated thymidine into fibroblasts which had been incubated with monocyte-conditioned medium obtained from monocytes of pigs treated with yellow phosphorus or bile duct-ligated rats and compared to the corresponding controls. Fibrosis was assessed by collagen content of liver sections obtained from the two animal models. The collagen content was determined by quantitation of Sirius red/Fast green-stained liver sections. In both animal models collagen content was significantly elevated at the conclusion of the treatment. Collagen content of liver sections of yellow phosphorus-treated animals were elevated (40 +/- 2.7, n = 15) compared to mineral oil-treated controls (23 +/- 1.2, n = 12) and collagen levels in the bile duct-ligated rat model liver sections were elevated (31.2 +/- 1.6, n = 6) compared to sham-operated controls (21.6 +/- 0.7, n = 6). The results of the fibroproliferation assay indicate that monocytes obtained from pigs treated with yellow phosphorus produce fibroproliferative factors during the development of fibrosis. This is in contrast to the bile duct-ligated rat model where no differences were observed in the production of fibroproliferative factors in the bile duct-ligated rats compared to sham operated controls suggesting that this may not be a key event in this model of fibrosis. Pentoxifylline treatment of the yellow phosphorus induced swine model of hepatic fibrosis has been associated with a marked improvement in fibrosis. In this study treatment of fibrotic pigs with pentoxifylline was associated with an improvement in liver function tests, a reduction of collagen content of liver sections, and reduction in fibroproliferation in pigs receiving yellow phosphorus treatment. Fibroproliferative factors were produced during the development of fibrosis in the swine model of fibrosis and their effect was blocked by pentoxifylline administered in vivo. This is in contrast to the bile duct-ligated rat model where pentoxifylline treatment was not associated with improvement in liver function tests or reduction of collagen content of liver sections and did not alter the fibroproliferative activity of monocyte-conditioned media. Taken together these results suggest that fibroproliferation and increased synthesis of collagen are key events in the yellow phosphorus-induced pig model of hepatic fibrosis and that the action of pentoxifylline in this animal model is likely to be related to its effects on fibroproliferation with a subsequent effect on collagen production. This is in contrast to the bile duct-ligated rat model where pentoxifylline does not prevent hepatic fibrosis.

Cytokine antagonists are a group of drugs defined by their actions on specific cytokines. Cytokine antagonists can inhibit action of cytokines by acting directly on receptors, by affecting production of cytokines or by binding to cytokines and preventing their subsequent action. Recent evidence suggests that Hansen's disease, which is characterized by reactional states, is associated with elevated serum levels of tumour necrosis factor-α (tnf-α) and interleukin-1β during these reactional states. Thalidomide, a drug used to treat reactional states in Hansen's disease, has been reported to enhance degradation of tnf-α mrna. Pentoxifylline has also been reported to alter tnf-α mrna levels by inhibiting tnf-a transcription. Combination of these two drugs as cytokine antagonists may prove to be beneficial as therapeutic agents in the treatment of reactional states in Hansen's disease. Pentoxifylline may prove to be beneficial in the treatment of reactional states in Hansen's disease patients who are female and of childbearing age. Cytokine antagonists alone or in combination will likely fill a niche in future therapeutics.

Platelet-derived growth factor (PDGF) stimulates fibroblast proliferation and increases collagen synthesis. Fibroproliferation, as assessed by tritiated thymidine uptake, was significantly stimulated by platelet-derived growth factor (8 ng/ml). Several drugs including dexamethasone (1 nM-20 microM), cysteamine (1.3-65 mM), N-acetylcysteine (0.6-15 mM), glutathione (1 microM-0.1 mM), glutathione peroxidase (0.1-1 Unit/ml), pentoxifylline (60 microM-36 mM), colchicine (0.025-250 nM) and aurothioglucose (1.15-23 microM) were assessed in the fibroproliferation assay for their ability to block the fibroproliferative effect of platelet-derived growth factor. Dexamethasone and aurothioglucose did not affect PDGF-stimulated fibroproliferation, while pentoxifylline, colchicine, cysteamine and N-acetylcysteine effectively reduced fibroproliferation stimulated by PDGF. The effect of pentoxifylline on PDGF stimulated fibroproliferation was compared to trapidil, theophylline and adenosine to assess mechanism of action. All four methylxanthines effectively inhibited PDGF stimulated fibroproliferation. Pentoxifylline was as effective as trapidil (IC50 = 129 microM and 141 microM, respectively), but pentoxifylline was more potent than theophylline (IC50 = 688 microM) and pentoxifylline was not as potent as adenosine (IC50 = 19 microM) in reducing PDGF-stimulated fibroproliferation.

Liver fibrosis is a complex process characterized by two major events: fibroproliferation and increased collagen synthesis. The exact role of cytokines in the pathogenesis of hepatic fibrosis remains to be established, but platelet-derived growth factor clearly stimulates proliferation of fibroblasts and increases collagen synthesis. In in vitro studies, pentoxifylline, a methylxanthine, significantly reduced platelet-derived growth factor-driven proliferation of fibroblasts. Platelet-derived growth factor has also been identified as a fibroproliferative factor produced spontaneously by monocytes obtained from patients with liver disease. Long-term administration of pentoxifylline (16 mg/kg orally, 5 days/wk for 12 wk) in an animal model of liver fibrosis prevented elevations in gamma-glutamyl transpeptidase and alkaline phosphatase levels and prevented the reduction in serum albumin level normally observed in this animal model of liver disease. The animal model used was a long-term, low-dose yellow phosphorus--induced model in pigs that reproducibly results in extensive fibrosis after 10 to 12 wk of treatment. Long-term administration of pentoxifylline also prevented the histological changes characteristic of fibrosis in this animal model. Collagen concentration was significantly elevated in liver sections obtained from animals receiving yellow phosphorus, compared with controls. Long-term pentoxifylline treatment resulted in significantly lower collagen concentrations in liver sections from animals receiving yellow phosphorus than in sections from animals receiving yellow phosphorus alone; this was supported by histological observation. Therefore administration of pentoxifylline prevented the biochemical and histological changes associated with an animal model of liver disease. Pentoxifylline will likely have an important therapeutic role in liver fibrosis.

Monocytes were isolated from blood of human origin and cultured in supplemented Leibovitz (L-15) medium for 24 hr. The medium was then decanted and filtered, and all subsequent tests were done on monocyte conditioned medium (MCM). The monocytes of patients with liver disease spontaneously secrete temperature-sensitive arylhydrocarbon hydroxylase (AHH) inhibitory factors detectable in the MCM. Anti-interleukin-1 antibody (IL-1Ab) reduced the AHH inhibitory activity of the MCM, suggesting that part of the AHH inhibitory activity was due to interleukin-1 (IL-1). Platelet derived growth factor did not affect AHH activity. Interleukin-1 beta was detectable in MCM but did not differ significantly between patients and normal volunteers. A time course experiment indicated that interleukin-1 beta inhibited hepatocyte AHH activity after only 2 hr of incubation. Catalase partially blocked the AHH inhibitory activity of MCM suggesting that activated oxygen intermediates are partially involved in the AHH inhibitory activity of the MCM. Simultaneous incubation of interleukin-1 beta and catalase did not prevent or augment the inhibitory action of IL-1 on AHH activity. IL-1 stimulates collagen synthesis and elevates serum procollagen type 3 peptide (P-III-P). Results indicated that serum P-III-P was elevated in blood sources producing temperature-sensitive AHH inhibitory factor.

Fibroproliferation was measured as the uptake of [3H]thymidine into fibroblasts. Human fibroblasts were incubated with 200 microliters monocyte-conditioned medium, the 0.22 microns filtrate from cultured monocytes, in Dulbecco's modified Eagle medium supplemented with controlled process serum replacement 2, a fetal calf serum substitute with low mitogenic activity. Increasing the numbers of fibroblasts resulted in a parallel increase in thymidine uptake to a maximal level. Fibroblasts (2 x 10(3] were plated into microwell plates and incubated with monocyte-conditioned medium for 72 hr. At 16 hr before harvest, 1 muCi [3H]thymidine was added. Cells were harvested with phosphate-buffered saline and washed, and the filters were counted. Fibroblasts incubated with Dulbecco's modified Eagle medium and controlled process serum replacement 2 showed minimal thymidine uptake. Fibroblasts incubated with Dulbecco's modified Eagle medium plus monocyte-conditioned medium from monocytes stimulated with 10 micrograms/ml lipopolysaccharides showed a sixfold increase in thymidine uptake over fibroblasts in Dulbecco's modified Eagle medium and controlled process serum replacement 2 alone. Fibroblasts incubated with Dulbecco's modified Eagle medium plus monocyte-conditioned medium from monocytes of patients with liver disease (n = 20) showed a 10-fold elevation in thymidine uptake compared with Dulbecco's modified Eagle medium and controlled process serum replacement 2. Results indicated that preincubation of monocyte-conditioned medium with either anti-interleukin-1 beta (12.5 half-maximal units, 4 degrees C, 16 hr) or catalase (1,870 IU, 25 degrees C, 1 hr) did not alter the fibroproliferative activity of the monocyte-conditioned medium, suggesting that neither interleukin-1 beta nor activated oxygen intermediates were involved in fibroproliferation.(ABSTRACT TRUNCATED AT 250 WORDS)