Subacute Inflammation Research Articles

Anti-inflammatory effect of petroleum ether extract of Vitex negundo leaves in rat models of acute and subacute inflammation

The anti-inflammatory effect of a petroleum ether extract of Vitex negundo Linn (Verbenaceae) leaves, (PEVNL) (250 and 500 mg/kg, p.o.), was evaluated in carrageenan-induced hind paw edema and cotton pellet granuloma models. Diclofenac sodium was used as a standard drug. The biochemical parameters were estimated in serum. In carrageenan-induced rat paw edema model PEVNL exhibited significant (p < 0.01) inhibition of edema volume at 4 h in a dose-dependent manner. In the cotton pellet granuloma model, dry weight of cotton pellets was significantly inhibited in a dose-dependent manner with maximum effect noticed at 500 mg/kg, p.o. Both doses of PEVNL were found to normalize the increased alkaline phosphatase, acid phosphatase, alanine amino transferase (ALT) and aspartate amino transferase (AST) and reversed the decreased serum albumin. In conclusion, PEVNL exhibited anti-inflammatory activity in acute and subacute models. At a dose of 500 mg/kg, p.o., PEVNL was found to possess maximum activity, and this effect was comparable with reference drug diclofenac sodium (5 mg/kg, p.o.).

Study conclusions should reflect results

Septic arthritis usually presents as subacute monoarticular inflammation. Majority of the cases in healthy adults are caused by methicillin-resistant <i>Staphylococcus aureus</i>, <i>streptococci</i> and certain gram-negative organisms, mostly in the setting of extremes of ages, trauma or immunosuppression. This is a case of a healthy adult with a sudden onset of inflammation of the knee joint, being diagnosed with septic arthritis of the left knee with <i>Veillonella</i> sp. growing from the joint aspirate on two successive cultures. The patient was treated with 6 weeks of oral metronidazole and 4 weeks of intravenous ceftriaxone in addition to arthroscopic drainage and irrigation. Rare causes of septic arthritis should be considered even in healthy adults with native joints. Closer follow-up might be needed to ensure successful treatment.

Cerebrospinal fluid study in paraneoplastic syndromes

Objective:Paraneoplastic neurological syndromes (PNS) probably result from an immune reaction against antigens shared by the nervous system and tumour cells. To characterise CSF alterations in these syndromes, we studied a...

The histopathology of involutional ectropion and entropion

Objective: Involutional ectropion and entropion are characterized by excessive horizontal eyelid length, which is thought to be secondary to laxity of the medial and lateral canthal tendons and to the stretching of the tarsus. Histopathological features of the surgical eyelid specimens from patients with involutional ectropion and entropion were evaluated. Design: Prospective histopathological study. Participants: Eighteen full-thickness eyelid specimens from patients with involutional ectropion and entropion were obtained during horizontal eyelid shortening procedures performed at the Ministry of Health Ankara Training and Research Hospital. Methods: All specimens were fixed in 4% formaldehyde solution and sectioned sagittally. Hematoxylin-eosin, periodic acid-Schiff, and Masson's trichrome staining were done for all specimens. Histopathologic alterations of the tarsal plate, the palpebral portion of the orbicularis muscle, and the conjunctiva were examined. Results: The patients ranged in age from 60 to 80 years. The main histopathologic features of the ectropic eyelids included collagen degeneration and elastosis of the tarsal plate, increased amounts of adipose tissue in the distal tarsus, and subacute inflammation and epidermalization of the tarsal conjunctiva. Specimens from patients with involutional entropion generally had milder degrees of these histopathological features. Conclusions: The causes of the excessive horizontal length of the eyelid, which is thought to be secondary to laxity of the medial and lateral canthal tendons, may be collagen degeneration and elastosis of the tarsal plate and canthal tendons.

Sometimes Less Is More: Perinatal Bacterial Exposure May Be More Important than Hepatitis for Liver Tumor Development

Vol. 116, No. 10 EnvironewsOpen AccessSometimes Less Is More: Perinatal Bacterial Exposure May Be More Important than Hepatitis for Liver Tumor Development David A. Taylor David A. Taylor Search for more papers by this author Published:1 October 2008https://doi.org/10.1289/ehp.116-a440bAboutSectionsPDF ToolsDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InRedditEmail Helicobacter hepaticus, a bacterium discovered in 1994 and widespread in many experimental mouse populations, is associated with a high incidence of liver tumors in aging mice. A new mouse study shows that perinatal exposure to this pathogen, rather than development of hepatitis itself, may be the single most important factor in the development of liver tumors caused by H. hepaticus[EHP 116:1352–1356; Diwan et al.]. The results support evidence from other studies that progressive hepatitis and liver tumors in older mice may stem from early-life exposure.The researchers isolated a strain of H. hepaticus from infected A/J mice. Female mice received injections with a single dose of the bacteria. Females testing positive for the bacteria were bred with uninfected males. The researchers assessed liver histopathologic findings and tumor growth in male offspring aged 2 weeks to 2 years. Uninfected weanling males from another lab were injected at 3–4 weeks.The results showed a significant incidence of liver tumors in the offspring after intraperitoneal maternal exposure to the bacteria: 33% developed liver tumors, usually multiple tumors, and 18% developed hepatocellular carcinoma. None of the mice injected with the bacteria as young adults developed any tumors.Another striking result was that tumor outcome was not closely linked to severity of hepatitis; mice that contracted hepatitis did not necessarily develop hepatic tumors. Rather, it appeared that early exposure to the bacteria, not the hepatitis itself, was key to fostering tumor growth.The type of additional perinatal event required to induce tumor development is unknown but could involve DNA damage at that vulnerable early stage, followed by subacute inflammation of the liver in response to H. hepaticus infection. The authors note that similar scenarios could apply to human infection with Helicobacter pylori and other pathogens linked with cancer. The results point to the need for further study of changes in perinatal tissues in response to such infections.FiguresReferencesRelatedDetails Vol. 116, No. 10 October 2008Metrics About Article Metrics Publication History Originally published1 October 2008Published in print1 October 2008 Financial disclosures License information EHP is an open-access journal published with support from the National Institute of Environmental Health Sciences, National Institutes of Health. All content is public domain unless otherwise noted. Note to readers with disabilities EHP strives to ensure that all journal content is accessible to all readers. However, some figures and Supplemental Material published in EHP articles may not conform to 508 standards due to the complexity of the information being presented. If you need assistance accessing journal content, please contact [email protected]. Our staff will work with you to assess and meet your accessibility needs within 3 working days.

Serum Concentration-Dependent Hepatotoxicity in Individuals Receiving Oral Salsalate

To the Editor, Salsalate, an older, ‘‘safer’’ oral nonsteroidal anti-inflammatory agent is a nonacetylated dimer of salicylic acid with an established safety profile in treatment of inflammatory conditions. It has been under consideration by the Food and Drug Administration (FDA) for over-the-counter (OTC) sale as an oral analgesic, antipyretic, and antirheumatic drug product since 1972. There is however, renewed interest in this drug as recent studies have shown that salsalate not only improves glycemic and inflammatory parameters in young obese adults but also improves body composition and metabolic alteration in human immunodeficiency virus (HIV) lipodystrophy by inhibiting nuclear factor kappa-B (NF-jB), a central integrator of proinflammatory signals [1, 2]. Since the product is inexpensive and generic, several National Institutes of Health (NIH)-funded clinical trials with salsalate are ongoing to test its effect on subacute inflammation and coronary plaque (TINSAL-T2D; NCT00624923), insulin resistance (NCT00330733), and bed-rest-induced vascular dysfunction (NCT00553995). The usual dosage for salsalate is 3,000 mg daily, given in divided doses. Some of the reversible adverse reactions reported in clinical trials such as tinnitus, nausea, hearing impairment, rash, and vertigo appear to occur more commonly with serum concentration above 30 mg/dl. Although a range of liver test abnormalities from asymptomatic elevation in transaminases to fatal fulminant hepatic failure have been reported with nonsteroidal anti-inflammatory drug (NSAID) use, data regarding salsalate specifically are sparse [4, 5]. These reactions were generally felt to be idiosyncratic in nature and independent of dose. We recently conducted a clinical trial using salsalate and wish to report our experience with salsalate-induced liver injury that exhibited a relationship with serum salsalate concentrations. In order to test the hypothesis that salsalate may improve the endothelial dysfunction that is frequently seen in patients with underlying HIV infection, we conducted a prospective study, approved by our institutional review board [3]. Eleven adults with documented HIV infection (CD4 count C 350/ll) not receiving any antiretroviral therapy and no known underlying liver disease were enrolled into this study. Each participant received 1,500 mg salsalate (Disalcid , 3M Pharmaceuticals, CA, USA) orally twice daily (the maximum daily dose approved by the FDA) with intended duration of treatment of 8 weeks. Serum liver chemistries, serum salicylate levels, and flow-mediated dilation of brachial artery (to measure endothelial function) were measured at baseline, and at 4 and 8 weeks after the initiation of salsalate treatment. The baseline characteristics were: mean age 37 ± 10 years, eight males, mean body mass index (BMI) 26.4 ± 7.8 kg/m, aspartate aminotransferase (AST) 25 ± 5 IU/l, alanine aminotransferase (ALT) 22 ± 9 IU/l, alkaline phosphatase 71 ± 18 IU/l, and total bilirubin 0.8 ± 0.3 mg/dl. During the study period, four patients developed elevated aminotransferases by 4 weeks following the initiation of salsalate whereas another seven participants exhibited no increase in liver biochemistries (Table 1). Two of the subjects with elevated aminotransferases had associated symptoms consisting of nausea, vomiting, fever, fatigue, and abdominal discomfort between weeks 2 and 3 after the initiation of therapy. Serum salicylate concentration measured 24–48 h after stopping the salsalate was R. Juluri S. Gupta R. Vuppalanchi (&) Division of Gastroenterology, Indiana University School of Medicine, 1050 Wishard Blvd., RG 4100, Indianapolis, IN 46202, USA e-mail: rvuppala@iupui.edu

Mild portal endotoxaemia induces subacute hepatic inflammation and pancreatic β‐cell dysfunction in rats

Portal endotoxaemia has been speculated to be crucially involved in the pathogenesis of chronic hepatic inflammation, which is highly associated with the development of type 2 diabetes mellitus. This study tests whether portal endotoxaemia is a pathogenic link between chronic subacute hepatic inflammation and pancreatic beta-cell dysfunction. Rats were randomly assigned into two groups: rats with intraportal saline or low-dose lipopolysaccharide (LPS) infusion for 4 weeks. Pathological changes in the liver were evaluated via histological and biochemical examination. Pancreatic insulin secretion was evaluated by in vivo hyperglycaemic clamp study. White blood cell count was significantly increased after intraportal LPS infusion for 4 weeks. Plasma amylase and chemoluminescence counts indicating superoxide levels were significantly increased after LPS treatments for 2 and 4 weeks. Intraportal low-dose LPS infusion significantly increased tumour necrosis factor-alpha and interleukin-6 contents in liver and pancreas. Circulating C-reactive protein, thiobarbituric acid reactive substances (TBARS) and endotoxin levels were not different among groups. The first- and second-phase insulin secretions in hyperglycaemic clamp were significantly decreased in LPS-treated rats. The histopathological scores, de novo production of reactive oxygen substrate and TBARS contents in the liver and pancreas were significantly increased in LPS-infused rats. Leucocyte infiltration was clearly visible in pancreatic islets of LPS-treated rats. The present study demonstrated that mild portal endotoxaemia caused subacute hepatic inflammation and impaired pancreatic insulin secretion, implicating that portal endotoxaemia is a potential risk factor to link chronic subacute hepatic inflammation and pancreatic beta-cell dysfunction.

Use of Salsalate to Target Inflammation in the Treatment of Insulin Resistance and Type 2 Diabetes

Chronic subacute inflammation is implicated in the pathogenesis of insulin resistance and type 2 diabetes. Salicylates were shown years ago to lower glucose and more recently to inhibit NF-kappaB activity. Salsalate, a prodrug form of salicylate, has seen extensive clinical use and has a favorable safety profile. We studied the efficacy of salsalate in reducing glycemia and insulin resistance and potential mechanisms of action to validate NF-kappaB as a potential pharmacologic target in diabetes. In open label studies, both high (4.5 g/d) and standard (3.0 g/d) doses of salsalate reduced fasting and postchallenge glucose levels after 2 weeks of treatment. Salsalate increased glucose utilization during euglycemic hyperinsulinemic clamps, by approximately 50% and 15% at the high and standard doses, respectively, and insulin clearance was decreased. Dose-limiting tinnitus occurred only at the higher dose. In a third, double-masked, placebo-controlled trial, 1 month of salsalate at maximum tolerable dose (no tinnitus) improved fasting and postchallenge glucose levels. Circulating free fatty acids were reduced and adiponectin increased in all treated subjects. These data demonstrate that salsalate improves in vivo glucose and lipid homeostasis, and support targeting of inflammation and NF-kappaB as a therapeutic approach in type 2 diabetes.

Environmental Stress, Erythrocyte Dysfunctions, Inflammation, and the Metabolic Syndrome: Adaptations to CO2 Increases?

In the Western world, the prevalence of the metabolic syndrome is increasing exponentially. Chronic subacute inflammation characterizes the syndrome, suggesting that inflammation might be a common denominator that links obesity to its pathologic sequelae. Potential mechanisms for the activation of inflammation include current air pollution inhalation and/or excess food intake. Both of these environmental factors have, in fact, been shown to promote oxidation followed by the release of proinflammatory cytokines. Potential sources of systemic inflammation include oxidized erythrocytes. Increased exogenous or endogenous CO2 deoxygenates hemoglobin, thereby increasing the fraction of hemoglobin reacting with nitrite to form methemoglobin together with release of superoxide and nitric oxide. These may form peroxynitrite, which may oxidize erythrocytes. Macrophages may then recognize and engulf these cells, thereby releasing proinflammatory cytokines. Therefore, studies should focus on the red blood cell and its proteins to finely target and appropriately treat a world pandemic ominously related to CO2 increases.

Histologie fonctionnelle du derme

The skin is composed of epidermis, dermis and subcutaneous tissue that interconnect anatomically. The dermis is an integrated system of fibrous and amorphous connective tissue that accommodates nerve and vascular networks, epidermally derived appendages, fibroblasts, macrophages and mast cells. Elastic and collagen tissue are the main types of fibrous connective tissue. The elastic connective tissue is assembled in a continuous network including mature elastic fibers, immature elaunin fibers and oxytalan fibers. Mature elastic fibers and elaunin have microfibrillar and amorphous matrix components while oxytalan fibers only contain microfibrils. Several molecules have been identified as constituents of the elastic fibers. Among the most characterized of these molecules is elastin in amorphous matrix, fibrillins 1 and 2 and LTBP-2 (ligand of latent TGFβ) in microfibrils and fibulins which interconnect elastin and fibrillins. Elastic fibers provides elasticity to the skin. Under electron microscope, collagen fibers appears as of bundles of periodically banded fibrils which are composed of collagens types I, III and V; type V collagen is believed to assist in regulating fibril diameter. They are associated with FACITs (fibril-associated collagen with interrupted triple helixes) collagens types XIV et XVI. Collagen fibers provide tensile strenght to the skin. Non fibrous connective tissue molecules include finely filamentous glycoproteins, glycosaminoglycans and proteoglycans of “the ground substance” (hyaluronic acid and chondroitin sulphate, dermatan sulphate, versican, decorin). Fibroblasts, macrophages and mast cells are regular residents of the dermis. The main function of these cells are well known. Fibroblasts are responsible for the synthesis and the degradation of fibrous and non fibrous connective tissue matrix proteins. Macrophages are phagocytic; they process and present antigen to immunocompetent lymphoid cells. Mast cells are responsible for IgE mediated acute, subacute and chronic inflammation. All these cells have a long list of other functions, in particular they are involved in coagulation, wound healing and tissue remodeling.

Toxicokinetic Study of Recombinant Human Heparin-Binding Epidermal Growth Factor-Like Growth Factor (rhHB-EGF) in Female Sprague Dawley Rats

To determine the toxicity and pharmacokinetics of recombinant heparin-binding epidermal growth factor-like growth factor in female Sprague Dawley rats following intra-bladder and intravenous administration. rhHB-EGF was administered once daily for 6 or 27 days at doses of 3, 10, or 30 microg/kg. 125I-rhHB-EGF was administered on day 7 or 28 for pharmacokinetic analysis. Toxicity was assessed by general appearance and behavior, gross necropsy, blood chemistry and microscopic evaluation. Plasma AUCss of [125I] rhHB-EGF equivalents following IB administration for 7 days were 4.28+/-2.29, 7.75+/-2.70, and 7.11+/-1.42 ng ml(-1) h(-1) at doses of 3, 10, and 30 microg/kg, respectively. Following IV administration, the AUCss on day 7 increased from 27.0+/-2.66 to 124+/-5.09 and 385.11+/-7.57 ng ml(-1) h(-1) with increasing the dose from 3 to 10 and 30 microg/kg. Similar AUCss data was obtained after 28 day administration. No toxicity was evident upon gross examination. Histologic examination revealed subacute inflammation and lymphocytic infiltration of the urinary bladder in animals from all groups dosed by the IB route. Plasma and bladder concentrations of recombinant human [125I] rhHB-EGF equivalents were significantly lower following the IB route than following IV administration. Histologic tissue examination indicated no toxicity attributable to rhHB-EGF.

A review of the biological and potential therapeutic actions of Harpagophytum procumbens

Harpagophytum procumbens (Hp), commonly known as Devil's Claw is a perennial plant which thrives in arid conditions. For centuries, it has been used as a traditional treatment for a variety of illnesses, including fevers, skin complaints, arthritis and diseases of the digestive tract as well as an appetite stimulant. Since its introduction to Europe in the early twentieth century, it has become a popular antiinflammatory and analgesic preparation amongst herbalists for supportive or adjuvant treatment of degenerative joint diseases, tendonitis, headache, backache and menstrual pain. The validity of Hp as an effective antiinflammatory and analgesic preparation, particularly in the relief of arthritic symptoms, has been investigated in numerous animal, clinical and in vitro studies. Although some contradictory evidence exists, the majority of animal studies appear to indicate Hp as an effective antiinflammatory and analgesic preparation in the treatment of acute and subacute inflammation. Clinical trials support Hp as a beneficial treatment for the alleviation of pain and improvement of mobility in a variety of musculoskeletal conditions. Analysis of the in vitro and ex vivo studies that currently exist, indicate that Hp has significant effects on numerous proinflammatory markers. However, the exact mechanism(s) by which Hp may reduce inflammation remain to be elucidated.

Anti-inflammatory Effect of Strychnos potatorum. Seeds on Acute and Subacute Inflammation in Experimental Rat Models

The anti-inflammatory effect of seed powder [SPP I (100 mg/kg) and II (200 mg/kg) p.o.] and aqueous extract [SPE I (100 mg/kg) and II (200 mg/kg) p.o.] of Strychnos potatorum. Linn (Loganiaceae) seeds was studied in carrageenin-induced hind paw edema and cotton pellet granuloma models. In carrageenin-induced rat paw edema model, both SPP (I and II) and SPE (I and II) exhibited mild inhibition at 1 h and maximum inhibition at 2.5 h in a dose-dependent manner. In the cotton pellet granuloma model, both wet and dry weights of the cotton pellets were significantly (p < 0.001) inhibited by SPP and SPE at both dose levels, whereas a maximum (p < 0.001) inhibition of wet and dry weights was found at 200 mg/kg, p.o. Both SPP and SPE were found to normalize the increased alkaline, acid phosphatases, and lipid peroxide levels indicating their membrane stabilization and free radical scavenging properties, respectively. In conclusion, both SPP (I and II) and SPE (I and II) exhibited anti-inflammatory activity in acute and subacute inflammatory models, whereas SPE-II was found to possess maximum activity and its effect was also comparable with the standard drug diclofenac sodium (5 mg/kg, p.o.).

Comparison of18F-fluoromethylcholine and 2-deoxy-D-glucose in the distribution of tumor and inflammation

The distribution characteristics of 18F-fluoromethylcholine (18F-choline) in tumor and inflammatory tissue were compared with those of 14C or 3H-2-deoxyglucose (2DG) as a substitute for fluorodeoxyglucose (FDG). A solid tumor model of AH 109A in the back of Donryu rats and an aseptic inflammation model of turpentine oil injection subcutaneously in rats were used for experiments. Tissue distribution was examined at 5, 30 and 60 min after injection of a mixture of 18F-choline and 3H-2DG. Double-tracer high-resolution autoradiographs (ARGs) of tumor and inflammation were obtained using 18F-choline and 14C-2DG. Whole body (WB) ARG was performed with 18F-choline. Tumor uptake of 18F-choline reached a peak at 30 min, when the tumor to blood ratio was 5.1. Both tumor and inflammation uptake of 2DG were higher than those of 18F-choline. 18F-choline uptake by inflammation was lower than that by tumor. The tumor to brain uptake ratio was 5.7 with 18F-choline and 1.2 with 2DG. In the ARG of inflammation, linear or ring-like structures of 2DG uptake were observed in the wall of the abscess, but were not identified with 18F-choline. Photomicrography showed that the uptake was limited to granulocytes, macrophages and fibroblasts, consistent with sub-acute or chronic inflammation. 18F-choline uptake by inflammation was lower than that of 2DG in the tissue distribution study, and 18F-choline uptake by abscess wall was significantly lower than that of 2DG in the autoradiography study. Our results may suggest the feasibility of 18F-choline-PET imaging for the differential diagnosis of cancer and chronic inflammation in lung and brain.

PL3 Stevens Johnson syndrome and mucous membrane pemphigoid: ocular manifestations and their management

Stevens Johnson Syndrome (SJS), its severe form Toxic Epidermal Necrolysis (TEN), and mucous membrane pemphigoid (MMP) are the major autoimmune causes of conjunctival scarring. Between them these diseases present some of the most difficult management problems in ophthalmology. SJS/TEN develop conjunctival disease as part of the acute generalised mucosal involvement. The conjunctivitis varies from a papillary reaction with watery discharge to a membranous conjunctivitis with sloughing of the conjunctival epithelium. Corneal epithelial defects are common and may progress to corneal ulceration with or without bacterial superinfection. Although the morbidity may be due to the acute corneal complications it more usually results from the progressive effects of the conjunctival scarring, the secondary ocular surface disease, infections &amp; treatment toxicity that occur later. Some cases of SJS/TEN develop the following late inflammatory diseases: recurrent conjunctival inflammation without scarring (recurrent SJS), inflammation with cicatrisation like ocular MMP (SJS‐MMP) and scleritis. On the other hand ocular MMP (MMPO) presents with acute conjunctivitis and limbitis in only 10% of cases; the remainder present with subacute or low grade chronic inflammation and progressive scarring. Progression in MMPO is due to the same factors that cause the morbidity in SJS/TEN (conjunctival scarring, the secondary ocular surface disease, infections &amp; treatment toxicity) coupled with the effects of the progressive conjunctival inflammation and scarring that is a feature of all cases of MMPO, but occurs in a few cases of SJS/TEN with ocular involvement. Successful management of both SJS/TEN and CP demands identification of the components of the disorder due to (i) surface disease, (ii) treatment toxicity (iii) immune mediated inflammation and (iv) infection. These problems lead to a dry eye, surface failure and corneal blindness. All these components of the problem require prompt treatment to prevent progression to surface failure because of the poor prognosis for rehabilitation, by corneal graft surgery and/or surface reconstruction, in this group of patients.

Background pathology of the common marmoset ( Callithrix jacchus) in toxicological studies

Two hundred common marmosets ( Callithrix jacchus) from control groups (100 males, 100 females) of toxicological studies were examined histopathologically to evaluate the spectrum of spontaneous lesions in this species. Frequent findings were extramedullary hematopoiesis affecting adrenal glands, liver, kidney and spleen, cystic Brunner's glands in the duodenum, acute or subacute inflammation in the large intestine and gall bladder, renal mineralization and pigmentation, hepatic Ito-cell vacuolation, microgranuloma and glycogen storage, pituitary cysts, C-cell hyperplasia and lymphocytic foci of the thyroid gland, luteal hyperplasia of the ovary and inflammatory cell foci in various organs.

Effect of aqueous extract ofTragia involucrata Linn. on acute and subacute inflammation

Antiinflammatory activity of aqueous extract of Tragia involucrata was tested on carrageenan-induced hind paw oedema and cotton pellet granuloma models in albino rats. In the subacute model, cotton pellet granuloma was produced by implantation of 10 mg sterile cotton in the axilla under ether anaesthesia. The animals were administered an aqueous extract at various concentrations of 50, 100, 200, 300 and 400 mg/kg. Phenyl butazone (80 mg/kg) was used as a standard drug. The paw diameter was measured at different time intervals and the dry granuloma weight was taken after the treatment. The aqueous leaf extract (400 mg/kg) showed the maximum inhibition (84.23%) of oedema at the end of 3 h following carrageenin-induced rat paw oedema. In subacute inflammation, the extract showed 76.25% reduction in granuloma weight. The results prove that the aqueous leaf extract showed highest antiinflammatory activity in acute and subacute inflammation and also support the usage of traditional claims.

Calcium enhances antiinflammatory activity of aspirin in albino rats

<b>Objective:</b> To evaluate the effects of calcium carbonate and calcium gluconate on acute and subacute inflammation, and to study their possible interactions with aspirin, verapamil and magnesium sulphate.<br><b> Materials and Methods: </b> Calcium carbonate in the dose of 10, 25, 50 mg/kg, calcium gluconate in the dose of 5, 10, 25, 50 mg/kg, and aspirin in the dose of 54, 200 mg/kg were administered orally in different groups of albino rats, to study their effect on inflammation induced by carrageenan or a foreign body. Aspirin (54 mg/kg) was administered either with calcium carbonate (10 mg/kg) or calcium gluconate (5 mg/kg) to separate groups in order to study their interaction, especially with reference to gastric ulceration. Similarly, possible interactions of verapamil (4 mg/kg) with calcium carbonate (10 mg/kg) and magnesium sulfate (500 mg/kg) with calcium carbonate (50 mg/kg) were also studied. <br><b> Results:</b> Both calcium carbonate and calcium gluconate produced significant antiinflammatory activity in acute as well as subacute inflammation models and was comparable to that of aspirin. Sub-antiinflammatory dose of calcium salts potentiated the antiinflammatory activity of aspirin. Verapamil also potentiated the anti-inflammatory activity of calcium carbonate while magnesium sulfate antagonized the antiinflammatory activity of calcium carbonate in both the models of inflammation.<br><b> Conclusion:</b> Co-administration of calcium salt potentiated the antiinflammatory response and minimized the gastro-toxicity of aspirin.

HMG-CoA Reductase Inhibitors: Effects on Chronic Subacute Inflammation and Onset of Atherosclerosis Induced by Dietary Cholesterol

Besides classical risk factors such as hypercholesterolemia and hypertension, chronic subacute inflammation has recently been recognized as an important force driving the development of atherosclerosis, the most common underlying cause of myocardial infarction and stroke. There is compelling evidence that a disturbance of cholesterol homeostasis contributes to the development of a chronic inflammatory state and that inhibitors of HMG-CoA reductase (statins) may dampen inappropriate inflammatory responses. We review the evidence and suggest mechanisms by which dietary cholesterol can induce an atherogenic inflammatory response in liver and vessel wall, with particular emphasis on the time course of this inflammatory response during atherogenesis and the interplay between these tissues. We discuss how statins interfere in this process, and whether they may reduce chronic subacute inflammation via a) their cholesterol-lowering effect, and/or b) their cholesterol-independent (pleiotropic) vasculoprotective activities. Recent studies performed in (humanized) animal models allow us to distinguish the lipid-lowering-dependent from the lipid-lowering-independent functions of statins. Using these data, we discuss the degree to which the lipid-lowering-dependent and lipid-lowering-independent effects of statins contribute to a reduction of inflammation, allowing estimation of the relevance of pleiotropic statin effects for the human situation.

Anti-inflammatory activity of Justicia prostrata gamble in acute and sub-acute models of inflammation

In this study, the aqueous (AQJP) and alcoholic (ALJP) extracts of the whole plant of Justicia prostrata Gamble (Acanthaceae) were screened for their acute and subacute anti-inflammatory activities using carrageenan-induced acute inflammation and cotton-pellet-induced granuloma (subacute inflammation), respectively, in rats. In the carrageenan-induced rat paw oedema model, both extracts were found to exhibit maximum reduction in paw volume at the first hour in a dose-dependent manner. At the dose of 500 mg/kg p.o., both extracts AQJP and ALJP showed maximum inhibition (51.39% and 62.5%, respectively) in rat paw oedema volume at the first hour of carrageenan-induced acute inflammation. In the cotton pellet granuloma assay, AQJP and ALJP at the dose of 500 mg/kg p.o. suppressed the transudative, exudative and proliferative phases of chronic inflammation. These extracts were able to (i) reduce the lipid peroxide content of exudates and liver and (ii) normalize the increased activity of acid and alkaline phosphatases in serum and liver of cotton pellet granulomatous rats. Preliminary phytochemical screening revealed the presence of lignans, triterpenes and phenolic compounds in ALJP, whereas phenolic compounds and glycosides in AQJP. The anti-inflammatory properties of these extracts may possibly be due to the presence of phenolic compounds. The anti-inflammatory effects produced by the extracts at the dose of 500 mg/kg, p.o. was comparable with the reference drug diclofenac sodium (5 mg/kg p.o.).