The Use of Bromfenac Ophthalmic Solution in Clinical Practice (Literature Review)

To this date nonsteroidal anti-inflammatory drugs play a huge role in the treatment of inflammatory eye diseases. Ophthalmologists face the question of choosing between glucocorticoid drugs (GCS) and nonsteroidal anti-inflammatory drugs (NSAIDs) for the treatment of any inflammatory process. At the same time, these groups can be used both in combinations and in monotherapy mode. Glucocorticoids are widely and effectively used in ophthalmology, but it should be remembered about a number of serious side effects of this group of drugs. When using these drugs, it is possible to increase ophthalmotonus, decrease the immune response and reparative processes, also GCS have cataractogenic and ulcerogenic effects, and therefore it careful use is necessary. NSAIDs are inferior to glucocorticoids in anti-inflammatory activity. Its mechanism of action is associated with blocking cyclooxygenase, inhibition of prostaglandin synthesis from arachidonic acid. In this regard, NSAIDs are the preferred group in the treatment of inflammatory eye diseases. The use of NSAIDs gives a good analgesic effect, this class of drugs is effective for the prevention of macular edema of various etiologies and reducing the risk of inflammation in the postoperative period. One of the most effective and most modern NSAIDs for topical use is a derivative of phenylacetic acid — Bromophenac, which in its formula has a bromine atom, which increases its lipophilicity, penetrating ability into the tissues of the eye, as well as analgesic and anti-inflammatory activity. Bromfenac is effective for relieving pain and all signs of inflammation caused by disease or surgery, suppressing the development of macular edema of various etiologies, has an antimiotic effect. Also, this group can be used after refractive surgery to reduce pain and photophobia, to relieve itching in allergic conjunctivitis. Double use of this drug during the day, the absence of discomfort and minimal side effects contribute to improving the patient’s compliance.

Change of Urinary Nitrite Excretion in Primary Enuresis after Indomethacin Treatment

Various treatment modalities have been used in primary Nocturnal Enuresis (PNE). Inhibition of prostaglandin synthesis may have value in the management of PNE. The effect of PGs on the urinary system are similar to those of Nitrous oxide (No), so there might be a link between No production and PNE. We can use nitrite as a good indicator of both PG and No because it is a stable metabolite of No. Our objective in this study was to assess urinary nitrite excretion in patients with enuresis and to evaluate the effect of indomethacin (a potent prostaglandin synthesis inhibitor) on urinary nitrite excretion. Sixty children participated in this study with age range 5-14 years and were divided into three groups: Group A comprised 20 children with PNE and were given 50 mg indomethacin suppositories each night for 1 month, group B comprised also 20 children with PNE not receiving treatment. Both groups were assessed by frequency of bed wetting episodes as well as by measuring urinary nitrites. In addition, 20 normal comparable controls were assessed as regards their urinary nitrites to show the difference in its values between enuretics and normal individuals. The results showed increase in nitric acid level in enuretic children than controls with marked decrease in its levels after receiving Indomethacin and marked improvement in the frequency of bed-wetting.

Poisons affecting the kidney

The kidney has an essential role in maintaining normal physiological functions but it can be affected by various drugs and chemicals. A common seasonal cause of renal failure in cats is ingestion of antifreeze containing ethylene glycol. It is not the ethylene glycol itself which causes renal failure but toxic metabolites which result in deposition of calcium oxalate crystals in the renal tubules. Various non-steroidal anti-inflammatory drugs, particularly those used in human medicine such as ibuprofen, flurbiprofen and naproxen, cause renal effects through inhibition of prostaglandin synthesis which results in reduced renal blood flow and disruption of normal renal function and homeostatic mechanisms. For some common substances, such as lilies in cats and grapes and their dried fruit in dogs, kidney injury occurs through unknown mechanisms. Management of poison-induced kidney injury is supportive with monitoring and support of renal function. Although haemodialysis and other extracorporeal techniques can be used, they are rarely available in veterinary medicine and therefore preventive measures are used. This includes aggressive intravenous fluid therapy before onset of signs for lily and grape poisoning and early use of the antidote (ethanol) in ethylene glycol poisoning to prevent formation of toxic metabolites, allowing excretion of the parent compound. In most cases, once kidney injury is advanced, prognosis is poor.

Effect of Organic Anion Transporters on the Development of Nephrotoxicity in the Context of NSAIDs Use

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used worldwide as pain relievers, antipyretics, and anti-inflammatory drugs. Failure to comply with the instructions for medical use of this group of drugs increases the risk of serious adverse reactions on the part of different organs and systems. From 5 to 18% of patients taking NSAIDs develop adverse reactions associated with impaired renal function. Organic anion transporter (OAT) proteins, which mediate the drug excretion with urine, have an important role to play in the NSAIDs adverse effect on kidneys. The aim of the study was to analyse and systematize scientific literature on the role of OATs in nephrotoxicity development in the context of NSAIDs use. It was revealed that adverse kidney reactions associated with NSAIDs are determined by several mechanisms, including inhibition of prostaglandin synthesis due to cyclooxeganse-1 and/or cyclooxeganse-2 blockade, and direct toxic effect on renal tubule epithelium followed by tubular necrosis due to NSAIDs interaction with OATs. Moreover, by suppressing OAT1 and OAT3, NSAIDs can not only enhance, but also reduce nephrotoxic effects of other medicines (when used together) and endogenous/exogenous toxins. Considering that NSAIDs are widely used in the treatment of various diseases (including in elderly patients and patients with concomitant renal diseases), it is still relevant to study mechanisms of adverse kidney reactions associated with drug transporters.

Antipyretic Activity of the Root Extracts of Xylocarpus

Various types of conditions exist in the body that causes fever and pain. Drugs that are used to treat fever are called antipyretics, and those are usually prescribed to treat elevated body temperature. But those drugs result in many other side effects like ulcers, perforations, bleedings and obstructions, which make their use questionable and limiting. Medicinal plants are used in the treatment of diseases from the starting of the human race and the process; they had been subjected to rigorous investigations and tests to establish a scientific proof and validation of the various pharmacological activities and their respective mechanisms of action in treating the herbs. Considering the anti-inflammatory properties of the plant, Xylocarpus mekongesis was investigated for its antipyretic activity in yeast method and 3doses out of which 00mg/kg body weight showed a better activity compared to the standard drug and other extracts too. The mechanism of action was similar to the paracetamol action that is inhibition of prostaglandin synthesis.

Poisons affecting the kidney

The kidney has an essential role in maintaining normal physiological functions but it can be affected by various drugs and chemicals. A common seasonal cause of renal failure in cats is ingestion of antifreeze containing ethylene glycol. It is not the ethylene glycol itself which causes renal failure but toxic metabolites which result in deposition of calcium oxalate crystals in the renal tubules. Various non-steroidal anti-inflammatory drugs (NSAIDs), particularly those used in human medicine such as ibuprofen, flurbiprofen and naproxen, cause renal effects through inhibition of prostaglandin synthesis which results in reduced renal blood flow and disruption of normal renal function and homeostatic mechanisms. For some common substances, such as lilies in cats and grapes and their dried fruit in dogs, kidney injury occurs through unknown mechanisms. Management of poison-induced kidney injury is supportive with monitoring and support of renal function. Although haemodialysis and other extracorporeal techniques can be used, they are rarely available in veterinary medicine and therefore preventive measures are used. This includes aggressive intravenous fluid therapy before onset of signs for lily and grape poisoning and early use of the antidote (ethanol) in ethylene glycol poisoning to prevent formation of toxic metabolites, allowing excretion of the parent compound. In most cases, once kidney injury is advanced, prognosis is poor.

Therapeutic Approaches of Resveratrol on Endometriosis via Anti-Inflammatory and Anti-Angiogenic Pathways

Endometriosis represents a severe gynecological pathology, defined by implantation of endometrial glands and stroma outside the uterine cavity. This pathology affects almost 15% of women during reproductive age and has a wide range of consequences. In affected women, infertility has a 30% rate of prevalence and endometriosis implants increase the risk of ovarian cancer. Despite long periods of studies and investigations, the etiology and pathogenesis of this disease still remain not fully understood. Initially, endometriosis was related to retrograde menstruation, but new theories have been launched, suggesting that chronic inflammation can influence the development of endometriosis because inflammatory mediators have been identified elevated in patients with endometriosis, specifically in the peritoneal fluid. The importance of dietary phytochemicals and their effect on different inflammatory diseases have been highlighted, and nowadays more and more studies are focused on the analysis of nutraceuticals. Resveratrol is a phytoestrogen, a natural polyphenolic compound with antiproliferative and anti-inflammatory actions, found in many dietary sources such as grapes, wine, peanuts, soy, berries, and stilbenes. Resveratrol possesses a significant anti-inflammatory effect via inhibition of prostaglandin synthesis and it has been proved that resveratrol can exhibit apoptosis-inducing activities. From the studies reviewed in this paper, it is clear that the anti-inflammatory effect of this natural compound can contribute to the prevention of endometriosis, this phenolic compound now being considered a new innovative drug in the prevention and treatment of this disease.

The Beneficial Biological Properties of Salicylic Acid

Summary Salicylic acid is a phytochemical with beneficial effects on human well-being. Salicylic acid is a phenolic compound and is present in various plants where it has a vital role in protection against pathogenic agents. Natural sources include fruits, vegetables and spices. The most famous and defined effect of salicylic acid is prostaglandin synthesis inhibition. Salicylic acid has antiinflammatory effects through suppression of transcription of genes for cyclooxygenase. Most of the pharmacological properties of salicylic acid can be contributed to the inhibition of prostaglandin synthesis. Also, it was discovered that salicylic acid has other in vivo cyclooxygenase-independent pathways. Since salicylic acid does not inhibit cyclooxygenase considerably, the anti-inflammatory effect is not a consequence of direct inhibition of cyclooxygenase activity. Because of its fundamental role, it was suggested that inhibition of nuclear factor kappa B by salicylic acid is one of the key anti-inflammatory mechanisms of action for salicylates. One of the most studied properties of salicylic acid is its antioxidative activity. Salicylic acid is a confirmed inhibitor of oxidative stress. Salicylic acid is capable of binding iron. This fact is significant for antioxidative effect of salicylic acid because iron has an important function in the course of lipid peroxidation.

Role of prostaglandins in determining the increased cardiac sympathetic nerve activity in ovine sepsis

Effective treatment of sepsis remains a significant challenge in intensive care units. During sepsis, there is widespread activation of the sympathetic nervous system, which is thought to have both beneficial and detrimental effects. The sympathoexcitation is thought to be partly due to the developing hypotension, but may also be a response to the inflammatory mediators released. Thus, we investigated whether intracarotid infusion of prostaglandin E2 (PGE2) induced similar cardiovascular changes to those caused by intravenous infusion of Escherichia coli in sheep and whether inhibition of prostaglandin synthesis, with the nonselective cyclooxygenase inhibitor indomethacin, administered at 2 and 8 h after the onset of sepsis, reduced sympathetic nerve activity (SNA), and heart rate (HR). Studies were performed in conscious sheep instrumented to measure mean arterial pressure (MAP), HR, cardiac SNA (CSNA), and renal SNA (RSNA). Intracarotid infusion of PGE2 (50 ng·kg−1·min−1) increased temperature, CSNA, and HR, but not MAP or RSNA. Sepsis, induced by infusion of E. coli, increased CSNA, but caused an initial, transient inhibition of RSNA. At 2 h of sepsis, indomethacin (1.25 mg/kg bolus) increased MAP and caused reflex decreases in HR and CSNA. After 8 h of sepsis, indomethacin did not alter MAP, but reduced CSNA and HR, without altering baroreflex control. These findings indicate an important role for prostaglandins in mediating the increase in CSNA and HR during the development of hyperdynamic sepsis, whereas prostaglandins do not have a major role in determining the early changes in RSNA.

Endocannabinoids and prostaglandins both contribute to GnRH neuron-GABAergic afferent local feedback circuits

Gonadotropin-releasing hormone (GnRH) neurons form the final common pathway for central control of fertility. Regulation of GnRH neurons by long-loop gonadal steroid feedback through steroid receptor-expressing afferents such as GABAergic neurons is well studied. Recently, local central feedback circuits regulating GnRH neurons were identified. GnRH neuronal depolarization induces short-term inhibition of their GABAergic afferents via a mechanism dependent on metabotropic glutamate receptor (mGluR) activation. GnRH neurons are enveloped in astrocytes, which express mGluRs. GnRH neurons also produce endocannabinoids, which can be induced by mGluR activation. We hypothesized the local GnRH-GABA circuit utilizes glia-derived and/or cannabinoid mechanisms and is altered by steroid milieu. Whole cell voltage-clamp was used to record GABAergic postsynaptic currents (PSCs) from GnRH neurons before and after action potential-like depolarizations were mimicked. In GnRH neurons from ovariectomized (OVX) mice, this depolarization reduced PSC frequency. This suppression was blocked by inhibition of prostaglandin synthesis with indomethacin, by a prostaglandin receptor antagonist, or by a specific glial metabolic poison, together suggesting the postulate that prostaglandins, potentially glia-derived, play a role in this circuit. This circuit was also inhibited by a CB1 receptor antagonist or by blockade of endocannabinoid synthesis in GnRH neurons, suggesting an endocannabinoid element, as well. In females, local circuit inhibition persisted in androgen-treated mice but not in estradiol-treated mice or young ovary-intact mice. In contrast, local circuit inhibition was present in gonad-intact males. These data suggest GnRH neurons interact with their afferent neurons using multiple mechanisms and that these local circuits can be modified by both sex and steroid feedback.