Analysis of the interaction between the HIV-inactivating protein cyanovirin-N and soluble forms of the envelope glycoproteins gp120 and gp41

The novel virucidal protein cyanovirin-N (CV-N) binds with equally high affinity to soluble forms of either H9 cell-produced or recombinant glycosylated HIV-1 gp120 (sgp120) or gp160 (sgp160). Fluorescence polarization studies showed that CV-N is also capable of binding to the glycosylated ectodomain of the HIV-envelope protein gp41 (sgp41) (as well as SIV glycoprotein 32), albeit with considerably lower affinity than the sgp120/CV-N interaction. Pretreatment of CV-N with either sgp120 or sgp41 abrogated the neutralizing activity of CV-N against intact, infectious HIV-1 virions. Isothermal calorimetry and optical biosensor binding studies showed that CV-N bound to recombinant sgp120 with a K(d) value ranging from 2 to 45 nM and to sgp41 with a K(d) value of 606 nM; furthermore, they indicated an approximate 5:1 stoichiometry for CV-N binding to sgp120 and a 1:1 stoichiometry for CV-N binding to sgp41. Circular dichroism studies additionally illuminated the binding of CV-N with both sgp120 and sgp41, providing the first direct evidence that conformational changes are a consequence of CV-N interactions with both HIV-1 envelope glycoproteins.     

Physiology and treatment of hypertension

Childhood hypertension (HT) is an increasing problem brought about by the epidemic of obesity. This is particularly true in adolescents, where currently Primary HT (PHT) is more common than secondary HT (SHT). The pathophysiology of PHT is complex and involves the interplay of genetic, congenital and environmental factors. It is important that every child with HT has a thorough evaluation so that any secondary cause of HT is identified and managed appropriately. There is increasing role for ABPM in the diagnosis and management of HT. Non-pharmacological therapy should be commenced on all children with hypertension and also those with high normal BP. The decision to initiate antihypertensive therapy should not be based on BP readings alone but should consider the presence or absence of end organ damage and other risk factors such as obesity, kidney disease and family history. Long term studies detailing the outcome of childhood HT and treatment are lacking. Since adult studies have demonstrated that treatment of hypertension leads to improved cardiovascular outcomes, it is imperative that HT is promptly diagnosed and appropriate treatment is commenced to prevent progression of end organ damage.     

Cross-linked protein crystals for vaccine delivery

The progress toward subunit vaccines has been limited by their poor immunogenicity and limited stability. To enhance the immune response, subunit vaccines universally require improved adjuvants and delivery vehicles. In the present paper, we propose the use of cross-linked protein crystals (CLPCs) as antigens. We compare the immunogenicity of CLPCs of human serum albumin with that of soluble protein and conclude that there are marked differences in the immune response to the different forms of human serum albumin. Relative to the soluble protein, crystalline forms induce and sustain over almost a 6-month study a 6- to 10-fold increase in antibody titer for highly cross-linked crystals and an approximately 30-fold increase for lightly cross-linked crystals. We hypothesize that the depot effect, the particulate structure of CLPCs, and highly repetitive nature of protein crystals may play roles in the enhanced production of circulating antibodies. Several features of CLPCs, such as their remarkable stability, purity, biodegradability, and ease of manufacturing, make them highly attractive for vaccine formulations. This work paves the way for a systematic study of protein crystallinity and cross-linking on enhancement of humoral and T cell responses.     

A prospective clinical review of ��multi model�� approach for treating ear keloids

This is a prospective clinical study of 46 ear keloids in 31 patients (with a mean follow-up of 18 months) treated from January 2006 to December 2006 at The Queen Elizabeth Public Hospital, Barbados, West Indies by a single surgeon. The mean age is 21.9 years (range 3-66 years). Seven out of 46 lesions were recurrent lesions following previous surgery. All the lesions were excised surgically (extralesional). Ten out of 31 patients were given postoperative, Intralesional Triamcinolone starting from the 1^st post operative visit on three visits at monthly intervals. Fourteen patients were given postoperative superficial X-ray therapy of 12 Gy in three equal fractions on three consecutive days starting from the 3^rd postoperative day. Seven recurrent keloids of this study were given a combination of both superficial X-ray therapy and intralesional triamcinolone. All patients were followed at monthly intervals for three visits from the time of surgery and every three months until the end of the 1^st year and then every six months thereafter. Five of 46 postoperative surgical wounds showed evidence of recurrence during the 1^st year but could be suppressed with Intralesional triamcinolone. This study confirms that surgical excision of keloids supplemented with radiotherapy and/Intralesional triamcinolone is a reliable method with few complications. In addition, the study concludes that the key in preventing recurrence is regular clinical follow-up to encounter early recurring lesion (clinical evidence of raised scars or palpable nodules if deep seated) which is 100% susceptible to Intralesional triamcinolone for 2-3 times at monthly intervals.     

Primary Meningoencephalitis by Naegleria fowleri: First Reported Case from Mangalore, South India

A fatal case of primary amebic meningoencephalitis (PAM) in a 5-month-old infant is described. The disease may have been contracted during bathing. The source of water was from an artificial well. The clinical presentation, the isolation of the ameba from the cerebrospinal fluid, the poor response to amphotericin B, and the ultimate fatal outcome are all consistent with the diagnosis of PAM. On the basis of its ability to grow at temperatures above 30 degrees C, the morphology of the trophozoite, and the presence of flagellate forms, the ameba was identified as Naegleria fowleri. Pathogenic N. fowleri amebae were recovered from samples of water from the well. To our knowledge this case represents the second case of PAM in an infant in the absence of the history of swimming.     

Post laryngectomy rehabilitation the case for planned early speech therapy

This study reflects the efficacy of planned early speech therapy on post laryngectomy rehabilitation. Not only do a larger number of laryngectomees acquire intelligible esophageal speech where therapy is instituted early but also the pace of development and quality of the speech is far superior when compared to those laryngectomees in whom speech therapy was delayed. This paper unequivocally supports the institution of planned early speech therapy in the successful rehabilitation of the laryngectomee. Such therapy can proceed simultaneously with the post operative radiation therapy sans deleterious effects and without prolonging hospital stay with its attendant overheads.     

Regulation of rat cardiac Kv1.5 gene expression by thyroid hormone is rapid and chamber specific.

Thyroid hormone affects the contractile and electrophysiological properties of the cardiac myocyte that result in part from changes in the expression of thyroid hormone-responsive cardiac genes, including those that regulate membrane ion currents. To determine the molecular mechanisms underlying this effect, expression of a voltage-gated K+ channel, Kv1.5, was measured in response to thyroid hormone. Using quantitative RT-PCR methodology, the content of Kv1.5 messenger RNA (mRNA) in left ventricles of euthyroid rats was 4.25+/-0.6x10(-20) mol/microg total RNA and was decreased by 70% in the hypothyroid rat ventricle to 1.27+/-0.80x10(-20) mol/microg RNA (P<0.01). Administration of T3 to hypothyroid animals restored ventricular Kv1.5 mRNA to control levels within 1 h of treatment, making this the most rapid T3-responsive cardiac gene reported to date. The half-life of Kv1.5 mRNA was 1.9 h and 2.0 h in euthyroid and hypothyroid ventricles, respectively, and T3 treatment of the rats did not alter its half-life. In atrial myocardium, expression of Kv1.5 mRNA (6.10+/-0.37x10(-20) mol/microg RNA) was unaltered by thyroid hormone status. The myocyte-specific and chamber-selective expression of Kv1.5 mRNA was confirmed in primary cultures of rat atrial and ventricular myocytes.