Antimicrobial, Wound Healing and Antioxidant Activities of Anthocephalus Cadamba

Anthocephalus cadamba (Roxb.) Miq. Syn A. chinensis (Lamk) A. Rich (Rubiaceae) is ethnomedicinally widely used in the form of paste by tribe in western Ghats for treating skin diseases. In this context, antimicrobial potential of A. cadamba against a wide range of microorganisms was studied. To validate the ethnotherapeutic claims of the plant in skin diseases, wound healing activity was studied, besides antioxidant activity to understand the mechanism of wound healing. The alchoholic and aqueous extract of this plant showed significant antibacterial and antifungal activity against almost all the organisms: Micrococcus luteus, Bacillus subtilis, Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, and four fungi Candida albicans, Trichophyton rubrum—dermatophyte fungi, Aspergillus niger, Aspergillus flavus and Aspergillus nidulans—systemic fungi, with especially good activity against the dermatophyte (Trichophyton rubrum) and some infectious bacteria (Escherichia coli, Proteus mirabilis and Staphylococcus aureus) with an MIC of 2.5 µg/disc. The results show that A. cadamba extract has potent wound healing capacity as shown from the wound contraction and increased tensile strength. The results also indicated that A. cadamba extract possesses potent antioxidant activity by inhibiting lipid peroxidation and increase in the superoxide dismutase (SOD) and catalase activity.     

Tear Break-up Time in High Altitude Areas

Background

In high altitude areas, patients report with irritation, redness and foreign body sensation in their eyes suggesting tear film abnormality due to low humidity and windy environmental conditions.

Methods

Tear Break- up Time (TBUT) was studied in 100 subjects consisting of local population and those originally from plains residing in high altitude areas in Ladakh.

Result

There were 24% individuals with TBUT of < 5 seconds, 30% between 6-10 seconds and 46% with TBUT of > 10 seconds. In symptomatic patients with TBUT of <5 seconds, eight cases had irritation of eyes, six foreign body sensation and two cases had pain, watering, irritation and redness of eyes. Pterygium was seen in 12 individuals and inter palpebral congestion in 4 cases. Conclusion: A total of 24% cases showed abnormal (<5 seconds) TBUT. Abnormality of tear film in the presence of low humidity and windy condition with high ultraviolet radiation may lead to ocular discomfort and pterygium in these areas.Key Words: Tear Break-up Time (TBUT), High altitude areas (HAA)     

Molecular requirements for inhibition of the chemokine receptor CCR8 – probe-dependent allosteric interactions

BACKGROUND AND PURPOSE

Here we present a novel series of CCR8 antagonists based on a naphthalene-sulfonamide structure. This structure differs from the predominant pharmacophore for most small-molecule CC-chemokine receptor antagonists, which in fact activate CCR8, suggesting that CCR8 inhibition requires alternative structural probes.

EXPERIMENTAL APPROACH

The compounds were tested as inverse agonists and as antagonists against CCL1-induced activity in Gα_i signalling and chemotaxis. Furthermore, they were assessed by heterologous competition binding against two radiolabelled receptor ligands: the endogenous agonist CCL1 and the virus-encoded antagonist MC148.

KEY RESULTS

All compounds were highly potent inverse agonists with EC₅₀ values from 1.7 to 23 nM. Their potencies as antagonists were more widely spread (EC₅₀ values from 5.9 to 1572 nM). Some compounds were balanced antagonists/inverse agonists whereas others were predominantly inverse agonists with >100-fold lower potency as antagonists. A correspondingly broad range of affinities, which followed the antagonist potencies, was disclosed by competition with [¹²⁵I]-CCL1 (K_i 3.4–842 nM), whereas the affinities measured against [¹²⁵I]-MC148 were less widely spread (K_i 0.37–27 nM), and matched the inverse agonist potencies.

CONCLUSION AND IMPLICATIONS

Despite highly potent and direct effects as inverse agonists, competition-binding experiments against radiolabelled agonist and tests for antagonism revealed a probe-dependent allosteric effect of these compounds. Thus, minor chemical changes affected the ability to modify chemokine binding and action, and divided the compounds into two groups: predominantly inverse agonists and balanced antagonists/inverse agonists. These studies have important implications for the design of new inverse agonists with or without antagonist properties.     

Immunodeficiency and infantile bone and joint infection

Fifteen patients with infantile bone and joint infections were studied immunologically and clinically, 3 at the time of illness and 12 later. Abnormality of immunoglobulins, or complement, or phagocytes was found in 9 patients; 6 were within normal limits for the tests undertaken. Immunodeficiency is probably responsible for the subdued clinical signs of infection and for delayed diagnosis in some patients. It was also related to the extent of femoral head damage in infective arthritis of the hip and to the incidence of wound infection in late elective surgery.     

Utility of myocardial performance index measured by left ventricular catheterization

BACKGROUND: Myocardial performance index (MPI) is a valuable index of global ventricular performance. It is almost always measured by Doppler echocardiography. The purposes of this study were (I) to compare MPI measured by catheterization (MPIc) and that measured by Doppler echocardiography (MPId), and (2) to compare it with the functional status. MATERIALS AND METHODS: The study included 80 patients who had undergone left heart catheterization.The MPIc was measured from the pressure recordings obtained at left ventricle and aorta. RESULTS: Mean MPId and MPIc were 0.40 +/- 0.12 and 0.42 +/- 0.12, respectively. Mean left ventricular end diastolic pressure (LVEDP) was 13 +/- 5 mm Hg. Mean heart rate was 77 +/- 11 beats/min. Mann-Whitney U test revealed that MPIc could discriminate between the functional statuses of the patients. The regression analysis revealed that there is a good correlation between MPIc and MPId, LVEDP or heart rate.There was no significant difference between MPIc and MPId (p > 0.05). CONCLUSION: The present data show that (I) the MPIc has a strong correlation with MPId; (2) it is a good discriminator of functional status. It may provide an additional information regarding the left ventricular performance in patients who underwent the cardiac catheterization.     

Long-term effects of beta blocker therapy on P-wave duration and dispersion in congestive heart failure patients: a new effect?

Atrial fibrillation (AF) is associated with heart failure in approximately 20%-50% of patients with increased morbidity and mortality. P-wave maximum duration (PWM) and P-wave dispersion (PWD) are recent ECG markers and reflect increased risk of AF. The aim of our study was to investigate the long-term effects of metoprolol on atrial conduction abnormalities as estimated by PWM and PWD, which were calculated on 12-derivation surface ECG in heart failure patients. Forty-two NYHA class 3 to 4 patients (23 males, 19 females and aged 52.9 +/- 11.2) were enrolled in the study. At the end of the 6 months, PWM and PWD values were significantly decreased (for PWM: from 115.2 +/- 12.6 to 105.4 +/- 13.5; for PWD: from 39.3 +/- 9.1 to 28.6 +/- 10.5; P <.001 for both). Metoprolol treatment is associated with a decreased duration of PWM and PWD and this may reflect a reduction in the probability of atrial fibrillation in heart failure patients.     

The effect of different combination therapies on oxidative stress markers in HIV infected patients in cameroon

The study assessed the effect of some highly active antiretroviral therapies (HAART), used in the management of HIV/AIDS in Cameroon, on oxidative stress markers such as malondialdehyde (as TBARs), albumin, protein carbonyl content and protein sulfhydryls groups. 85 HIV positive patients (34.8 ± 9.3 years) were on three different highly active antiretroviral therapies (HAART patients). 65 HIV positive patients (32.2 ± 10.9 years) on no treatment (Pre-HAART patients), and 90 non-HIV infected patients (32.6 ± 9.3 years), were the control groups. Plasma TBARs as well as carbonyl levels were significantly higher in HIV patients on HAART compared to pre-HAART patients or non-HIV infected controls. On the other hand, the protein sulfhydryl group content was not different for patients on HAART compared to pre-HAART patients, but both were significantly lower than non-HIV infected controls (P < 0.0001, 0.001). The combination treatment Therapy I [stavudin (80 mg) + Lamivudin (600 mg) + Nevirapin + (400 mg) zidovudin (600 mg)] brought about a significant (p < 0.05) reduction in the plasma concentration of protein sulfhydrl groups as well as TBARs compared to Therapy II [stavudin (80 mg) + Lamivudin (300 mg) + nevirapin (400 mg)] or with combination Therapy III of [zidovudine (600 mg) + lamivudin(300 mg) with efavirenz (600 mg)] (P < 0.05). The content of the antioxidant, Vitamin C was lower in the plasma of patients on Therapy I compared to those on Therapy II (P < 0.01) and Therapy III (P < 0.001).