Evaluation of the anticonvulsant and muscle relaxant effects of the methanol root bark extracts of Annona senegalensis

ObjectiveTo investigate the potentials of the root bark of Annona (A.) senegalensis in the control of seizure and related hypnotic and motor incoordination effects in mice using experimental models.MethodsThe methanol extract (ME) of the root bark of A. senegalensis was studied in mice using pentylenetetrazole (PTZ) induced convulsions, phenobarbitone induced sleeping time and motor coordination test on rota-rod performance. Acute toxicity and lethality (LD₅₀) test as well as phytochemical analysis were also carried out.ResultsThe extract (200, 400, 800 mg/kg) exhibited a non-dose dependent significant (P <0.05) delay in the onset of both tonic and clonic phases of seizure induced by PTZ (60 mg/kg, s.c.) as well as offered a 100% protection (200 mg/kg) in mice from PTZ induced seizures. The extract significantly (P <0.05) decreased the latency and increased the duration of phenobarbitone induced sleeping time. At 200 mg/kg, the extract exhibited a significant (P <0.05) motor incoordination. The acute toxicity test revealed an oral LD₅₀ of 1 296 mg/kg, while the phytochemical studies showed the presence of alkaloids, resins, glycosides, carbohydrate, reducing sugar, flavonoids, terpenoids, saponins and tannins.ConclusionThe extract of A. senegalensis possessed anticonvulsant activity with pronounced hypnotic and muscle relaxant effects.     

CYP11β1 (11-beta-hydroxylase) deficiency in congenital adrenal hyperplasia

Objective : To review experience of CYP11β1 deficiency (previously known as 11β-hydroxylase) at the Royal Children's Hospital, Melbourne, Victoria.
Methodology : A retrospective case review was conducted from 1974 to 1995 with five cases identified.
Results : Age of presentation ranged from 1 day to 7 years. Presentation was with ambiguous genitatia at birth (two females), simple virilization (two males) and suspected early puberty in mid childhood (one female). Associated clinical features were hypertension (three cases) and tall stature with markedly advanced bone age (four cases). Biochemical abnormalities consistent with CYP11β1-deficiency were elevated urinary tetrahydro-11-deoxycortisol ( n = 5) and elevated serum 11-deoxycortisol ( n = 3). Additional abnormalities were elevated 17-hydroxyprogesterone ( n = 3), elevated androstenedione ( n = 4) and elevated dehydroepiandrosterone sulphate ( n = 4). The clinical features and investigations suggested CYP11β1-classical deficiency in four patients and CYP11β1-non-classical deficiency in one patient.
Conclusions : The five cases of CYP11β1-deficiency demonstrate a spectrum of clinical abnormalities, with diagnostic difficulties in two cases and delayed presentation in three cases. Prompt diagnosis of CYP11β1-deficiency is facilitated greatly by the availability of a gas chromatography-mass spectrometry instrument and is essential to avoid the long-term effects of hypertension and hyperandrogenism.     

The Angiographic Findings in a Haemophilic Pseudotumour of Bone

The angiographic findings in a patient with haemophilic pseudotumour of the femur are presented. The examination showed the position of the displaced femoro-poplited vessels, enabling these structures to be avoided at operation. Under anti-haemophilic globulin cover no complications occurred. It is suggested that angiography may be safely employed provided the coagulation defect is controlled. The examination may be useful in differentiating other bone lesions and in defining more clearly the extent of a haemophilic pseudotumour.     

Macrophage depletion induced by clodronate-loaded erythrocytes

Given the important role of macrophages in various disorders, the transient and organ specific suppression of their functions may benefit some patients. Until now, liposome-encapsulated bisphosphonate clodronate has been extensively proposed to this end. In this paper, we demonstrate that erythrocytes loaded with clodronate can also be effective in macrophage depletion. Here, clodronate was encapsulated in erythrocytes through hypotonic dialysis, isotonic resealing and reannealing to final concentrations of 4.1 +/- 0.4 and 10.1 +/- 0.8 micromol/ml of human and murine erythrocytes, respectively. The ability of clodronate-loaded erythrocytes to deplete macrophages was evaluated both in vitro and in vivo. In vitro studies on human macrophages showed that a single administration of engineered erythrocytes was able to reduce cell adherence capacity in a time-dependent manner, reaching 50 +/- 4% reduction, 13 days post treatment. The administration of loaded erythrocytes to cultures of murine peritoneal macrophages was able to reduce macrophage adhesion 67 +/- 3%, 48 h post treatment. In vivo, the ability of clodronate-loaded erythrocytes to deplete macrophages was evaluated both in Swiss and C57BL/6 mice. Swiss mice received 125 microg of clodronate through erythrocytes and 6 days post treatment 69 +/- 7% reduction in the number of adherent peritoneal macrophages and 75 +/- 5% reduction in number of spleen macrophages were observed. C57BL/6 mice received 220 microg clodronate by RBC and 3 and 8 days post treatment 65 +/- 7% reduction in the number of spleen macrophages and the complete depletion of liver macrophages were obtained. In summary, our results indicate that clodronate selectively targeted to the phagocytic cells by a single administration of engineered erythrocytes is able to deplete macrophages, even if not completely. The transient suppression of macrophage functions through clodronate-loaded erythrocytes can be used in many biomedical phenomena and research applications.     

Human immunodeficiency virus infection and acquired immunodeficiency syndrome dementia complex: role of cells of monocyte-macrophage lineage

The entry of human immunodeficiency virus (HIV) into the central nervous system (CNS) causes both the establishment of a lifelong viral reservoir in the brain and symptoms of neurological dysfunction that have an AIDS dementia complex (ADC) clinical appearance. Neurological dysfunction in ADC patients still remains an unresolved problem. However, ADC pathogenesis may be a multistep process that starts with HIV invasion of CNS by crossing the blood-brain barrier (BBB). It progresses by developing a chronic inflammatory status that can cause dysfunction in neurons and astrocytes that result in apoptotic death. Monocytes-macrophages (M/M) may play an important role by concealing the HIV transfer across the BBB. Furthermore, HIV-infected M/M could produce and release neurotoxic factors. In this review the main mediators and cells involved in pathogenesis and development of ADC are highlighted. A better understanding of the mechanisms involved in this process may help in a successful therapeutic approach to the neuropathogenesis of HIV infection.     

Potent antiviral activity of amprenavir in primary macrophages infected by human immunodeficiency virus

Objective of the present study was then to assess the antiviral activity of the protease inhibitor amprenavir in macrophages (M/M), and to compare it with its efficacy in peripheral blood lymphocytes (PBL). M/M were obtained from blood of sero-negative healthy donors and infected with M-tropic HIV-1 strain (HIV-1(Ba-L)). The stabilized infection was assessed by monitoring the HIV-1 p24 gag antigen production in the supernatants of M/M cultures. In the setting of acute infection (treatment before HIV-1 challenge), amprenavir showed substantial activity both in M/M and PBL at similar concentrations (EC(50): 0.011 and 0.031 microM, respectively); complete inhibition of HIV-1 replication was achieved in both cell types at concentration of about 2 microM. In the setting of chronical infection (i.e. antiviral treatment several days after established infection), an antiviral effect of amprenavir was achieved in M/M, but at concentrations higher than those active in acutely infected M/M (EC(50): 0.72 microM, EC(90): 18.2 microM). The antiviral effect in chronically infected M/M was sustained for at least 2 weeks of continuous treatment. These findings suggest that amprenavir (at relatively high concentrations) has a clinically relevant antiviral effect in persistently infected reservoirs of HIV.     

Ancestry reported by white adults with cutaneous melanoma and control subjects in central Alabama

Background  

We sought to evaluate the hypothesis that the high incidence of cutaneous melanoma in white persons in central Alabama is associated with a predominance of Irish and Scots descent.