Gamete development inPlasmodium berghei regulated by ionic exchange mechanisms

Ionic regulation in the induction of exflagellation ofPlasmodium berghei was investigated by culturing the parasites in various isotonic media. Of the salts tested, NaHCO₃ exhibited the highest activity in inducing exflagellation, whereas KHCO₃ showed no activity. In the absence of HCO ₃ ^– , media containing monovalent cation (Na⁺, K⁺, Cs⁺, Rd⁺, choline⁺, lysine⁺, arginine⁺) and Cl^– also induced exflagellation, but their activities were lower than that of NaHCO₃. Anions of Br^– or NO ₃ ^– could be substituted with Cl^–, whereas other anions such as I^–, NO ₂ ^– , SO ₄ ^2– , SCN^–, H₂PO ₄ ^– , or HPO ₄ ^2– failed to induce exflagellation, as did tetramethylammonium-Cl, CaCl₂, MgSO₄, MgCl₂ and sucrose as well. These results suggest that the induction of exflagellation requires the presence of Na⁺ and HCO ₃ ^– or monovalent, membrane-permeable cation and Cl^– in the medium. Measurements of the efflux of H[¹⁴C]O ₃ ^– or Cl^– indicated that these anions were released from the cells into the NaCl or the NaHCO₃ medium, respectively, probably by exchange in HCO ₃ ^– /Cl^–. Determination of intracellular ionic concentrations by electron microscopic X-ray microanalysis of cryopreserved specimens revealed that in the NaHCO₃ medium, external Na⁺ (and probably HCO ₃ ^– ) enters the gametocytes by exchange with internal Cl^– (and probably H⁺), whereas in Cl^–-containing media, external unspecified cation and Cl^– influx by exchange, probably with H⁺ and HCO ₃ ^– . It is therefore suggested that two separate ion exchangers, i.e., Na⁺-dependent HCO ₃ ^– (in)/Cl^–(out) and nonspecific monovalent-cation-dependent Cl^–(in)/HCO ₃ ^– (out) exchangers, are involved in the induction of gametogenesis inP. berghei. Furthermore, the presence of both classes of anion in the medium enhanced exflagellation activity and increased Na⁺ uptake more than did the NaCl or NaHCO₃ medium alone. The apparent synergistic enhancement by two contraactive anion exchangers is consistent with a recycling model of pH_i regulation, in which HCO ₃ ^– and Cl^– are exchanged between the cells and the media, resulting in the acceleration of monovalent cation/H⁺ exchange.This work was supported by a Grant-in-Aid (No. 01570212) from the Ministry of Education, Science and Culture, Japan and the Ohyama Health Foundation, Japan (to FK), and in part by the Medical Research Council, United Kingdom (to RES)     

Louse-borne relapsing fever: II. Combined penicillin and tetracycline therapy in 160 Sudanese patients

One hundred and sixty patients with louse-borne relapsing fever were treated with a combination therapy of procaine penicillin and tetracycline. Fortified procaine penicillin B.P. was given as 400,000 units in the first day. This was followed the next day by 2 g tetracycline orally in divided doses for seven days. A mild rise in temperature was observed in 22 (13·7%) patients within four hours of administering penicillin. Rigors and hypotension occurred in one patient. Relapse occurred in two patients, of whom one had concomitant typhoid and one visceral leishmaniasis. The combined therapy has been found to be effective and safe. It lacks the disadvantages of penicillin (relapses) and tetracycline (severe reaction), when each drug is used alone.The use of the arsenicals (Wolffet al., 1946; Garnhamet al., 1947), penicillin (Taft & Pike, 1945; Ingraham & Lepenta, 1946; Harrison & Whittington, 1951; Knaacket al., 1972) and tetracycline (Brycesonet al., 1970; Knaacket al., 1972) in louse-borne relapsing fever has resulted in a dramatic reduction of the mortality rate from more than 40% in untreated cases (Garnhamet al., 1947) to less than 5%. However, each of these drugs suffers from one drawback or another. The arsenicals are toxic (Wolffet al., 1946). Penicillin is slow in clearing the spirochaetaemia, has a higher rate of relapse and does not clear residual infection in the brain (Harrison & Whittington, 1951). Tetracycline almost invariably induces a distressing Jarisch-Herxheimer reaction (Brycesonet al., 1970; Knaacket al., 1972; Perineet al., 1974). The combined use of penicillin (to reduce reaction) and tetracycline (to prevent relapses) can be a safe and effective alternative in the treatment of this disease. This paper describes the treatment of 160 Sudanese patients with louse-borne relapsing fever, using combined penicillin and tetracycline.     

The trouble with kidneys derived from the non heart-beating donor: a single center 10-year experience

BACKGROUND: The demand for renal transplantation has increasingly outstripped the supply of donor organs especially over the past 10 years. Although related and unrelated live donation is being promoted as one option for increasing the donor pool, it is unlikely that this will in itself be able to bridge the gap. Non-heart beating donors (NHBD) can provide an alternative supply of organs, which should substantially increase the donor pool. METHODS: In Newcastle, NHBD kidneys have been used for transplantation for a period of 10 years. In the early period (1988-1993) excellent results were obtained (90.5% success); however, these donors were controlled NHBD, Maastricht category III. In the second phase (1994-1998) increasing numbers of donors were obtained from the Accident and Emergency Department unit. These were failed resuscitation for cardiac arrest (category II). The rates of success in this period were poor (45.5% success) and the program was halted. The third phase of the program used machine perfusion of the kidneys and glutathione S transferase enzyme analysis to assess viability. RESULTS: Using such approaches renal transplants from largely category II donors produced a success rate of 92.3% which was significantly better than the phase II period of the program (P=0.023, Fisher two-tail test). CONCLUSION: Machine perfusion and viability assessment of NHB kidneys in phase III of the program has increased our donor pool as well as improved the graft survival. This is particularly relevant for the use of the category II NHB donor where the incidence of primary nonfunction was high, illustrated by phase II where machine perfusion/viability assessment was not used.     

Segmental myoclonus as the presenting symptom of an acute disseminated encephalomyelitis: a case report.

Segmental myoclonus is described as the involuntary contractions of contiguous muscles innerved by the brain stem or by spinal cord. The underlying causes of segmental myoclonus in children are demyelinating diseases and intrinsic tumors. Here, we report a case who was presented with segmental myoclonus on his left arm and later diagnosed as atypical monosymptomatic presentation of acute disseminated encephalomyelitis (ADEM). The case represents the first in the literature in which ADEM is considered as the possible cause of segmental myoclonus. Our findings demonstrate that: (i) in focal movement disorders such as segmental myoclonus, a careful neuroradiological examination of the neuroanatomical region for the possible presence of organic lesions might be rewarding, (ii) ADEM might be one of the potentially reversible causes of myoclonus.     

Prognostic significance of metastasis-associated protein S100A4 (Mts1) in prostate cancer progression and chemoprevention regimens in an autochthonous mouse model.

PURPOSE: We recently showed that metastasis-promoting Mts1 gene (S100A4) and protein is overexpressed during progression of prostate cancer in humans. The purpose of this study was to assess the expression of S100A4 during autochthonous prostate cancer progression in transgenic adenocarcinoma of the mouse prostate (TRAMP) model. Because oral consumption of green tea polyphenols (GTP) has been shown to inhibit metastasis and prostate cancer in TRAMP, we further assessed the significance of S100A4 during chemoprevention regimen. EXPERIMENTAL DESIGN: Male TRAMP mice 8 weeks of age were equally divided into two groups. A freshly prepared 0.1% GTP solution in tap water was supplied thrice a week to experimental animals as the sole source of drinking fluid for 24 weeks, whereas the control group of animals received the same tap water throughout the experiment. The animals were sacrificed at 0, 8, 16, and 24 weeks of GTP feeding and were analyzed for S100A4 and E-cadherin. Additional untreated and treated nontransgenic controls were also included in the study. RESULTS: With the progression of age and prostate cancer growth in TRAMP mice, an increase in the expression of S100A4 at mRNA and protein level in dorsolateral prostate, but not in nontransgenic mice, occurred. GTP feeding to TRAMP mice resulted in marked inhibition of prostate cancer progression, which was associated with reduction of S100A4 and restoration of E-cadherin. CONCLUSIONS: S100A4 represents a promising marker for prostate cancer progression and could be employed as a biomarker in chemoprevention regimens.