Aminophylline targeting to lung: optimization of the size and drug loading of albumin microspheres.

Aminophylline, a bronchodilator, was considered a suitable drug for targeting to the lung to treat emphysema. Factorial concept was utilized to optimize the size and drug loading of microspheres suitable for targeting. Aminophylline-loaded albumin microspheres were prepared by heat denaturation adjusting the manufacturing variables, namely albumin concentration, drug concentration, water-oil phase ratio and stirring rate at low and high levels. For two levels of the four variables the experimentation was performed in 16 batches. A good yield of well-defined microspheres of the size range, 2-30 microns, were obtained from all the batches. The drug loading was found maximum (36.33 per cent) in batch XV of microspheres prepared with low albumin concentration, high drug concentration, low water-oil phase ratio and low stirring rate. The least number (13 per cent) of microspheres of batch XV were below 7 microns and the remaining 87 per cent were above this size. Considering the payload and size, microspheres of batch XV were found suitable for targeting to the lung.     

Characterization of GP110, a neutrophil surface protein.

Localized juvenile periodontosis is associated with a defect of neutrophil chemotaxis that is characterized by selective depletion of a surface protein with a molecular mass of 110 kDa (GP110). Data on partial characterization of GP110 suggest that it is a glycoprotein which is enriched in Lys, Glu, His, Leu, and Ala residues.     

Clinical profile of AIDS: a study at a referral hospital

The present study describes the clinical and epidemiological features of 74 patients with human immunodeficiency virus (HIV) infection who presented to a referral hospital. Sixty two patients (83.7%) were diagnosed to have acquired immune deficiency syndrome (AIDS). Mean age of the patients was 34.9 +/- 12 years and male to female ratio was 3:1. Majority of patients (80%) were from lower socio-economic class. Multiple unprotected heterosexual contact with commercial sex workers in metropolitan cities of India, mainly Mumbai, was major risk factor in 82.1% male patients while most of the females (66.6%) had acquired infection from HIV positive husbands. Blood transfusion was the risk factor in 9(12.1%) patients. Sixty eight patients were infected with HIV 1, one with HIV 2, and five patients with both HIV 1 and HIV 2. Fever and weight loss were the commonest presenting symptoms. Tuberculosis, oropharyngeal candidiasis, and interstitial pneumonitis were present in 54.8%, 40.3% and 20.9% patients, respectively. Fourteen patients (22.5%) had generalised lymphadenopathy. Herpes zoster, cryptococcal meningitis, and peripheral neuropathy were infrequent. Response to standard antifungal and antitubercular treatment was satisfactory. Kaposi's sarcoma, lymphoma, and CNS toxoplasmosis were not found. The clinical manifestations of AIDS patients are strikingly different from that in the Western countries. It, thus, necessitates setting up of different guidelines for the clinical diagnosis and management of AIDS in India.     

Hepatic microsomal cytochrome P450 system during experimental hookworm infection

Experimental infection of golden hamsters with the hookworm, Ancylostoma ceylanicum, caused a profound decline in the hepatic microsomal cytochrome P450 content. Concomitant decrease was also noticed in aminopyrine N-demethylase and benzo[a]pyrene hydroxylase activities. However, aniline hydroxylase activity was only marginally elevated during the infection. Microsomal markers, viz., cytochrome b5, NADH-cytochrome-c reductase, and glucose-6-phosphatase, were not significantly altered. Hepatic tissue exhibited an accumulation of lipids, especially phospholipids, triglycerides, and cholesterol, resulting in fatty necrosis around the central vein region. Isolated hepatic microsomes showed a decrease in phosphatidylcholine content. Impairment in hepatic mixed function oxidase (MFO) activities was further confirmed by prolongation in hexobarbital sleeping time and zoxazolamine-induced paralysis. The hepatic MFO system of A. ceylanicum-infected hamsters responded qualitatively and quantitatively in a manner similar to that of control hamsters, upon stimulation with selective chemical inducers like phenobarbitone and 3-methylcholanthrene. Kinetic and in vitro substrate binding studies revealed that for aminopyrine the substrate affinity and the maximum enzyme activity (Vmax) were decreased, while for aniline the binding affinity was decreased and the binding capacity was enhanced. Results indicate specific/selective impairment of the hepatic microsomal cytochrome P450 system during hookworm infection and may have many practical implications in toxicology and pharmacology.     

Validity of self-report of recent opiate use in treatment setting

Self-report validity of recent drug use among heroin abusers depends on many factors including the population being studied and the setting in which the study is carried out. This study was conducted by the treating physicians to assess the self-report validity of recent heroin use by heroin dependent patients in the outdoor setting using 'thin layer chromatography' (TLC) and two highly sensitive methods of urinalysis viz. 'gas liquid chromatography' (GLC) and 'high performance liquid chromatography' (HPLC). Out of seventy-six heroin dependent patients who entered the study, 64 provided urine sample on the same day. Patients' self-report about recent opiate use was found to have a moderate agreement with urinalysis report. However, it is important to validate it with urinalysis during the treatment process because a substantial proportion of patients fails to report recent opiate use. It is recommended that all drug dependence treatment centres should be equipped with a sensitive urinalysis facility. Otherwise, the outcome of the treatment process should be considered with caution.     

Stimulation of human monocytes by anti-CD3 monoclonal antibody: Induction of inflammatory mediator release via immobilization of Fc receptor by adsorbed immunoglobulin and T-lymphocytes

Human monocytes released superoxide anion, prostaglandin E₂, leukotriene B₄, IL-1, and TNF when exposed to plastic surfaces coated with murine anti-CD3 monoclonal antibody, OKT 3. Stimulation of mediator release by OKT 3 was dependent on the amount of antibody immobilized onto wells of plastic tissue culture plates. Soluble antibody or antibody adsorbed to monocytes and reacted with an aggregating (cross-linking) second antibody failed to induce mediator release. Monocytes armed with OKT 3 formed rosettes with T cells in a fashion indistinguishable from that seen between monocytes and T cells sensitized with OKT 3. Monocytes with adsorbed OKT 3 antibodies released IL-1 and TNF- when exposed to unsensitized T cells, although increased superoxide release could not be detected. OKT 4a, a murine IgG_2a antibody that reacts with a different T cell epitope (CD4), failed to induce cytokine release from monocytes when cross-linked by T cells or a CD4+ T cell line, even in the presence of IL-2 or IFN-. These data indicate that certain antibodies bound to Fc receptors (FcR) of monocytes may trigger monocyte function when reacting with cells bearing the appropriate target antigens. FcR-mediated signaling resulting in mediator release may be involved in initiating or regulating the immune response. Furthermore, systemically administered monoclonal antibodies may induce inflammatory responses and their attendant symptomatologies via their interaction with FcR-bearing inflammatory cells.     

Malignant nasal paraganglioma: a case report and review of the literature

A rare case of malignant nasal paraganglioma is described. A 30 year old female patient presented with a one year history of bilateralnasal obstruction, nasal deformity and recurrent epistaxis. CT scan demonstrated an enhancing mass occupying both nasal cavities, right maxillary antrum and anterior ethmoid sinus. Histopathologic diagnosis was malignant paraganglioma. A total maxillectomy with excision of growth was performed. Post-operative radiotherapy and chemotherapy was given but patient expired before the completion of therapy. Nose being a rare site for paragangliomas, these lesions present a diagnostic challenge to histopathologists and clinicians alike. A review of the four previously described malignant nasal paragangliomas is also presented.