Pharmacology Journal

Cyclosporin A (CSA) is a uniquely potent immunosuppressant used world-wide to sustain organ transplantation. It has also been proven effective in a variety of autoimmune and related disorders. However, dose-dependent side-effects, particularly at the level of the kidney, may ultimately define the limits of clinical utility of the drug because they frequently mandate modification of therapy to avoid chronic renal insufficiency. The first site of nephrotoxicity is vasoconstriction at the efferent and afferent glomerular arterioles. The second site is cellular hypoxia. Both effects may add to impair renal function, but cellular ischemia occurs independently from vasoconstriction as cellular ischemia can be reproduced in vitro in renal cells as well as in isolated mitochondria of these renal cells. A major effect of CSA is to promote calcium accumulation in the mitochondrial matrix. Read more…

Spinal muscular atrophies (SMA) are characterized by degeneration of motoneurons of the anterior horn of the spinal cord, leading to progressive symmetrical limb and trunk paralysis associated with muscular atrophy. It is a rather frequent inherited disease (1 in 6000 newborns). SMA have been divided into three clinical forms depending on the clinical severity: type I (Werdnig-Hoffmann disease, early onset of weakness, death occuring during the first year of life); type II (intermediate); and type III (Kugelberg-Welander disease, late onset of weakness, patients remaining ambulant).

The gene responsible for SMA has been mapped to 5q11.2–9-q13.3, and subsequently identified as survival motor neuron [SMN]. This region contains an inverted duplication of a 500-kb element, leading to two duplicate inverted copies of SMN, so-called telomeric and centromeric SMN (SMN^tel and SMN^cent, respectively). The predicted proteins encoded by both genes are identical, although the sequences of their genes differ by 5 nucleotides. Read more…

Angiotensin-converting enzyme (ACE) inhibitors, such as enalapril, captopril and lisinopril, are drugs of choice for the treatment of hypertension and congestive heart disease in humans and dogs. Their use results notably in a lowering of blood pressure, without the adverse effects (decreased cardiac function and lipid metabolism) observed with some other vasodilators acting on the central nervous system. Yet it has been reported that in 1–33% of patients, these drugs can induce airway hyperreactivity and chronic dry cough.

The cough reflex is usually viewed as being elicited by stimulation of irritant receptors with myelinated afferent fibers, called rapidly adapting stretch receptors (RARs). It appears, however, that unmyelinated C-fibre endings may be involved. Inhaled capsaicin, predominantly a C-fibre ending stimulant, can cause coughing in humans and guinea pigs. This response involves sensory mechanisms, as it can be inhibited in guinea pigs by pretreatment with high doses of capsaicin, causing degeneration of sensory nerves. C-fibres contain tachykinins such as substance P, which can be released upon the action of citric acid]. Tachykinin receptor antagonists can inhibit the citric acid-induced cough reflex. The receptor types involved in the reaction depend on the species. Read more…

Regardless of the cause, intestinal ischemia is a serious and growing clinical problem with an unacceptable mortality rate over 60%. When blood flow to the intestine is decreased, mucosal lesions develop in the upper part of the villi and during reperfusion, development of these lesions is rapid.

Formation of toxic oxygen metabolites has been suggested to play an important role in the development of damage during ischemia/reperfusion (I/R) injury. Oxygen radical formation results in damage to an array of biomolecules found in tissues, including nucleic acids, membrane lipids, enzymes and receptors. Membrane-associated polyunsaturated fatty acids are readily attached by reactive oxygen species in a process that results in the peroxidation of lipids. Peroxidation of membrane lipids disrupts membrane fluidity and cell compartmentation, which can result in cell lysis. Thus, oxygen radical-initiated lipid peroxidation and protein damage may contribute to the impaired cellular function and necrosis associated with reperfusion. Read more…

Thiazide diuretics have long since been used for the treatment of severe hypertension. They are effective in inhibiting sodium transport at the distal tubule in the mammalian nephron and hence decrease water retention. One of the most widely used thiazide diuretics is hydrochlorothiazide (HCTZ; 6-chloro-3,4-dihydro-2H-1,2,4-benzothiadazine-7-sulfonamide 1,1-dioxide). With a 65–75% oral absorption and an elimination half-time of about 2.5 h, HCTZ is still one of the most effective diuretics used in clinics to lower blood pressure and is even used as a monotherapy. It is known, however, that in the long term, thiazide diuretics appear to reduce blood pressure by reducing peripheral resistance rather than by their diuretic effects, suggesting a direct vascular dilating action. This action was also demonstrated in rabbits and dogs. Read more…

Globalclimate change has become one of the most important recent issue. Themajor contributor is the burning of fossil-fuels and deforestationwhich release large amounts of carbon-dioxide [].The consequences of man-induced global-scale climatic change have thepotential to trigger serious international economic and politicalevents for all nations. Thus any possible changes in the energyinfrastructure to encourage a reduction of fossil-fuels usage areimportant in meeting the challenge of climate change in connection withthe greenhouse effect.Coal, which has great importance among theenergy sources, is the primary factor for the industrial revolution inthe world. Countries that exploited their coal reserves in the thcentury are now developed countries. Coal keeps its favourable positionbecause it is a safe and reliable energy source, not only because coalrepresents about two-thirds of the entire world’s fossil energyresources, but its distribution is widespread.BP []indicates that the world’s oil reserves to production R/P ratio is. years, gas . years while coal years, i.e., nearly fourtimes that for oil and . times that for gas. With higher prices foroil and natural gas making coal more competitive, coal was again theworld’s fastest-growing used fuel in , with global consumptionrising by % per annum or twice the -year average.The increased use of coal will inevitably result in more air and water pollutions and rising global COemissions. BP statistics indicates that coal discharges . tonscarbon per ton of oil equivalent, while natural gas and oil is . and. tons respectively. In , coal was the second largestsource of world CO emissions behind oil and ahead of natural gas [].The major difficulty of dealing with man-induced climate change and the release of CO is directly related to energy use and future energy demands. COemissions have been clearly linked to economic growth. The world energyeconomy is carbon based: without question, no nation is prepared toreduce substantially or control CO emissions at least forthe foreseeable future. This does not mean that the formulation of along-term energy or environmental policy should be delayed [].Whatcan the world community do about it? Is it necessary to abandon theburning of coal to protect the Earth from unprecedented climate change?What realistic strategies can be followed to balance economic growthand environmental protection?Although coal has played a decisiverole in maintaining and promoting the steady growth of the worldeconomy, coal consumption patterns and trends in the Organization forEconomic Cooperation and Development OECD countries are muchdifferent from those outside the OECD i.e., non-OECD countriescountries.The Kyoto Protocol, which requires participatingcountries to reduce their carbon-dioxide emissions collectively to anannual average of about five percent below their level over the– period, became a legally-binding treaty on February , [].Coal consumption patterns in participating OECD and non-OECD countrieswill inevitably be effected. Will coal consumption reduction causeeconomic shocks? Is there a “causal” relationship between coalconsumption and economic growth? This paper considers the major OECDUnited States USA, Japan JP, South Korea KR and non-OECDcountries PR China CN, Russian Federation RF, India IN and SouthAfrica SA Table [] to study the causal relationships between coal consumption and economy and so provide a scientific basis for decision-making.Table . Coal Consumption of major OECD and non-OECD countries MTOE Change over share of total OECD countries United States..%.% Japan..%.% Germany.−.%.% South Korea..%.% Total OECD..%.% Non-OECD countries PR of China..%.% Russian Federation..%.% India..%.% South Africa.−.%.% Total non-OECD..%.%

AlthoughIndia, in recent years, is emerging as an industrial nation,agriculture remains a key sector in India’s economy, contributing about% of the gross domestic product and employing % of its adultpopulation ICID, . Annual agricultural growth has been modest at .% per annum over the last years IDNP, a.The average Indian farmer is a smallholder owing less than ha ofcultivable land, harvesting one crop a year and striving to harvest asecond crop Pangare et al., .Development plans of the Government of India and State Governments givepriority to alleviate poverty and to create employment, particularly inrural areas. Agriculture depends largely on the monsoon; rains,however, are unevenly distributed in time and space. To sustainagricultural production against these vagaries of rainfall, irrigationhas been created in about million ha, covering about %of the total arable land ICID, .The introduction of irrigated agriculture, however, has resulted in thedevelopment of the twin problem of waterlogging and soil salinization.Considerable areas have either gone out of production or areexperiencing reduced yield. With the misconception, that the more theyirrigate, the more yield they will get, farmers apply huge quantitiesof canal water, e.g. in Segwa, one of the study areas, the actualsupply of mm/year by far exceed the crop water requirementsof mm/year, based on a % application efficiency Ritzema et al., .Furthermore, the introduction of canal irrigation not only brings themuch-needed water, but also imports salts as irrigation water containsconsiderable amounts of salt. In Segwa, the canal water has a salinityof . dS m−, thus an irrigation gift of mm/year will add . t ha−of salts to the soil profile. It is estimated that nearly. million ha of the irrigated lands are affected by soilsalinity and alkalinity, of which about . million ha isalso waterlogged IDNP, a.Drainage,as a tool to combat waterlogging and salinity, has not been givenimportance as much as irrigation by the individual farmers as well asthe governmental agencies. In only about . million ha ofthe affected lands some sort of drainage system has been installed ICID, .Subsurface drainage was introduced only recently. Most systems are lessthan years old and widespread adoption did not take place Gupta, . So far subsurface drainage systems have been installed in about ha Nijland et al., .For the prevailing conditions in India, subsurface drainage systemswith rather deep drains, i.e. drain depth >. m, arerecommended Gupta, . Thisrecommendation is based on the critical depth concept, i.e. to avoidsecondary salinization caused by the upward flux of water once thewater table rises to – m below the soil surface Gupta and Gupta, .These deep drains have their drawbacks. Firstly, the deeper the drain,the higher the installation cost. Secondly, deep drains can onlyeconomically be installed by mechanical construction practices,ignoring the huge employment needs of the rural poor. Thirdly, deepdrains lower the water table during the irrigation season. These lowerwater tables reduce the rate of capillary rise and thus increase theburden on the already poorly performing irrigation systems. Research incountries with similar conditions, i.e. Egypt and Pakistan, indicatesthat shallower drains can maintain salinity levels within safe limitsfor crop production Abdel-Dayem and Ritzema, and Ritzema et al., .Research conducted in various agro-climatic regions in India alsosuggested that the drain depth can be reduced, although the recommendeddrain depth/spacing combinations vary considerably between the variousagro-climatic regions Table .Although sound theories now form the basis of modern drainage systems,there will always remain an element of art in land drainage. It is notpossible to give beforehand a clear-cut theoretical solution for eachand every drainage problem: sound engineering judgement on the spot isstill needed, and will remain so Bos and Boers, .To develop location-specific guidelines for subsurface drainage, theGovernments of India and The Netherlands jointly initiated theIndo-Dutch “Network Operational Research Project on Drainage and Water Management for Control of Salinity and Waterlogging in Canal Commands” IDNP, a. The recommendations and strategies developed by this project are presented in this paper.Table . Recommended drain depth-spacing combinations for various agro-climatic regions in India Agro-climatic regionDrain depth mDrain spacing mReferences Semi-arid coastal plains of Andhra Pradesh.–Rao Semi-arid Trans-Gangetic plains of Haryana.–.–Rao et al. and Achthoven et al. Humid coastal plains of Kerala.Mathew et al. Semi-arid plains of Gujarat.–Parikh et al. Arid lands of Rajasthan.–.–Aheer et al. and RAJAD Sub-humid regions of the lower Gangetic plains in West Bengal.–Rao

Juxtaglomerular (JG) cells are located in renal afferent arterioles close to the glomerulus. Here they are able to sense fluctuations in systolic pressure, ion composition in tubular fluid detected by the adjacent macula densa cells, sympathetic influences and hormonal influences, and respond by secreting renin. During development, renin expression in the primitive vessels of the fetal kidney gradually shrinks from the entire length of the afferent arteriole, to a more restricted length in the neonate and in the adult becomes confined just to the JG cells proximal to the glomerulus. ¹ This reflects the important role of renin in kidney development, where targeted renin gene deletion or pharmacological blockade of the renin–angiotensin system results in renal pathology and abnormal morphology. ^2,3 Under stimulatory conditions such as renal artery stenosis, hydronephrosis, low salt diet or blockade of angiotensin II formation, reactivation of renin expression occurs in a subset of medial cells of the larger renal arteries. ^4–6 In the adrenal, renin is maximal at day 15 postcoitus and later retracts to the zona glomerulosa. ⁷ Furthermore, low salt plus enalapril switches on renin mRNA in rat heart. Read more…