Studies on the mechanism of bacterial resistance to complement-mediated killing. II. C8 and C9 release C5b67 from the surface of salmonella minnesota S218 because the terminal complex does not insert into the bacterial outer membrane

The mechanism for consumption of terminal complement components and release of bound components from the surface of serum-resistant salmonella minnesota S218 was studied. Consumption of C8 and C9 by S218 occurred through interaction with C5b67 on the bacterial surface because C8 and C9 were consumed when added to S218 organisms previously incubated in C8-deficient serum and washed to remove all C5b67 on the bacterial surface because C8 and C9 were consumed when added to S218 organisms previously incubated in C8- deficient serum and washed to remove al but cell bound C5b67. Rapid release of (125)I C5 and (125)I C7 from the membrane of S218 was dependent on binding of C8 because (125)I C5 and (125)I C7 deposition in C8D serum was stable and was twofold higher in C8D than in PNHA, and addition of purified C8 or C8 and C9 to S218 previously incubated in C8D serum caused rapid release of (125)I C5 and (125)I C7 from the organism. Analysis by sucrose density gradient ultracentrifugation of the fluid phase from the reaction of S218 and 10 percent PNHS revealed a peak consistent with SC5b-9, in which the C9:C7 ratio was 3.3:1, but the NaDOC extracted bound C5b-9 complex sedimented as a broad peak with C9:C7 of less than 1.2:1. Progressive elution of C5b67 and C5b-9 from S218 but not serum-sensitive S. minnesota Re595 was observed with incubation in buffers of increasing ionic strength. Greater than 90 percent of the bound counts of (125)I C5 or (125)I C9 were released from S218 by incubation in 0.1 percent trypsin, but only 57 percent of (125)I C9 were released by treatment of Re595 with trypsin. These results are consistent with the concept that C5b-9 forms on the surface of the serum-sensitive S. minnesota S218 in normal human serum, but the formed complex is released and is not bactericidal for S218 because it fails to insert into hydrophobic outer membrane domains.     

Cervicogenic headache

Eleven female patients with cervicogenic headache (mean age, 43 years; range, 25-59 years) have been examined with the pupillometer. The pupillary diameter was examined in the basal state (that is, the status before pharmacologic stimulation) and after topically administered tyramine (2%), phenylephrine (1%), and hydroxyamphetamine (1%). A total of 51 tests were performed, 35 in the asymptomatic period and 16 during pain attacks. In a control group consisting of 26 age-matched women a total of 39 tests were carried out. Before pharmacologic stimulation (that is, in the "basal state") the pupils were smaller in the asymptomatic (pain-free) period than during pain attacks in the patients and also as compared with that of control individuals. The anisocoria (the difference in pupillary size in the same individual) observed was not significantly different between the patient group and control individuals either in the basal state (before pharmacologic stimulation) or after pharmacologic stimulation. The mydriasis resulting from the instillation of the three sympathicomimetic drugs was symmetrical in both controls and patients both during and between the pain attacks. This finding is in clear contrast to what is found in cluster headache, in which there is a "Horner-like" syndrome on the symptomatic side. These two headaches thus seem to differ essentially with regard to this variable.     

Purinergic receptors on insulin-secreting cells

Summary— The insulin secreting B cell is fitted with the two types of purinergic receptors: P₂ (for ATP and/or ADP) and P₁ (for adenosine). The activation of P₂ purinoceptors by ATP or ADP evokes a biphasic stimulation of insulin secretion from isolated perfused rat pancreas; this stimulation is dose-dependent between 10^?6 and 10^?4 M. Non hydrolysable structural analogues are also effective, and the relative potency of various agonists (2-methylthio ATP ? ATP = ADP = α, β-methylene ATP ? AMP) gave evidence for a P_2y purinoceptor subtype. Proposed mechanisms include both an increased Ca²⁺ uptake and an increased intracellular Ca²⁺ mobilization via the hydrolysis of polyphosphoinositides. ATP (or ADP) potentiates physiological insulin-secreting agents (glucose and acetylcholine) and P₂ purinoceptors could play a physiological role in the stimulation of insulin secretion. The activation of P₁ purinoceptors (adenosine receptors) decreases insulin secretion. Using structural analogues of adenosine, the receptor was characterized as an A₁ subtype; it is coupled to a pertussis toxin sensitive G protein and it inhibits adenylate cyclase. It is of physiological relevance that the B cell has the two types of purinoceptors with opposite effects. Recently, a metabolically stable structural analogue of ADP, adenosine-5′-0-(2-thiodiphosphate) or ADPßS, has been described as a potent secretory agent, effective at nanomolar concentrations on isolated perfused rat pancreas. In vivo, this substance is able to increase insulin secretion and to improve glucose tolerance after IV administration in rats and oral administration in dogs. Furthermore in streptozotocin-induced diabetes, ADPßS retains its insulin secreting effects. These results suggest that P_2y purinoceptors could be a new target for antidiabetic drugs.     

INTRACEREBRAL HAEMORRHAGE IN A YOUNG ADULT: CONSIDER AMPHETAMINE ABUSE

SUMMARY We present the case of a young female who suffered a massive intracerebral bleed following the ingestion of a small quantity of amphetamine (speed). Physicians should be aware that amphetamine abuse can lead to cerebrovascular events in young adults.     

Adrenaline,Noradrenaline and Dopamine Level Estimation in Depression : Does it Help?

Background

Abnormalities of catecholaminergic function have been hypothesised in causation of depressive illness. Electroconvulsive therapy (ECT) is postulated to have noradrenergic mechanism of action. We studied the clinical utility of estimating catecholamines level changes after ECT.

Methods

Plasma adrenaline, noradrenaline and dopamine in healthy controls and depressed patients were estimated by high performance liquid chromatography with electrochemical detection method before and after ECT.

Result

Mean ± standard deviation of plasma adrenaline, noradrenaline and dopamine in controls was 36.7 ± 13.2, 209.3 ± 76, 21.8 ± 9.5 ng/L respectively, while in depressed patients before and after ECT it was found to be 32.5 ± 12.0, 419.3 ± 167.7, 22.1 ± 16.0ng/ L and 37.2 ± 19.6, 386.1 ± 168.4, 22.3 ± 15.5ng/L respectively. Correlation of adrenaline, noradrenaline and dopamine concentration with scores of Beck Depression Inventory, Suicidal Ideation Scale and Melancholia Inventory was positive but statistically not significant and poor. Based on the cut off values of noradrenaline, only 62% cases could be categorized as abnormal, which after ECT reduced to 50%, whereas post ECT psychiatric ratings was normal in about 78% cases.

Conclusion

There is no clinical significance of estimating adrenaline, noradrenaline and dopamine in depressed patients.Key Words: Electroconvulsive therapy, Adrenaline, Noradrenaline, Dopamine, Psychiatric scales