STUDIES ON MECHANISM OF INSULIN CONVULSIONS* EFFECTS OF VARYING PARTIAL PRESSURES OF ATMOS- PHERIC OXYGEN AND CARBON DIOXIDE IN ADRENALECTOMIZED ANIMALS

In the course of the preceding study concerning the effects of various procedures on the serum electrolytes and on the occurrence of insulin convulsions in the normal dog, it was found that convulsive reactivity was markedly decreased by reducing the oxygen or by increasing the carbon dioxide tension of the atmosphere (1). When no insulin was administered, breathing a gaseous mixture composed of 88 to 95 per cent nitrogen and 12 t0 5 per cent oxygen caused significant reductions in the potassium and inorganic phosphorus as well asin the carbon dioxide tension of the serum, but no other electrolyte changes. .     

The effect of the bite plane splint on the electromyographic silent period duration

An electromyographic study of the masseter and anterior part of the temporalis muscles was performed on ten patients presenting temporomandibular joint dysfunction symptoms. The EMG silent periods (SP) produced in the open-close-clench cycle and jaw-jerk reflex were compared for duration before and after treatment with an occlusal bite splint. Following use of the splint, there was a shortening of SP indicating the possible use of the duration of SP as a diagnostic measurement, and also as an indication of treatment effectiveness.     

Left Ventricular Mechanical Assist Devices and Cardiac Device Interactions: An Observational Case Series

Background: Nonpulsatile left ventricular assist devices (LVADs) are increasingly used for treatment of refractory heart failure. A majority of such patients have implanted cardiac devices, namely implantable cardioverter-defibrillators (ICDs) or cardiac resynchronization therapy-pacemaker (CRT-P) or cardiac resynchronization therapy-defibrillator (CRT-D) devices. However, potential interactions between LVADs and cardiac devices in this category of patients remain unknown.
Methods: We reviewed case records and device logs of 15 patients with ICDs or CRT-P or CRT-D devices who subsequently had implantation of a VentrAssist LVAD (Ventracor Ltd., Chatswood, Australia) as destination therapy or bridge to heart transplantation. Pacemaker and ICD lead parameters before and after LVAD implant were compared. In addition, ventricular tachyarrhythmia event logs and potential electromagnetic interference reports were evaluated.
Results: Right ventricular (RV) sensing decreased in the first 6 months post-LVAD. Mean R-wave amplitude preimplant was 10.9 ± 5.25 mV compared with 7.2 ± 3.4 mV during follow-up (P = 0.02). RV impedance also decreased from 642 ± 240 ohms at baseline to 580 ± 212 ohms at follow-up (P = 0.007). There was a significant increase in RV stimulation threshold following implantation of the LVAD from 0.8 ± 0.6 V at baseline to 1.4 ± 1.0 V in the first 6 months postimplant (P = 0.01). A marked increase in ventricular tachyarrhythmia burden was observed in three patients. One patient displayed electromagnetic interference between the LVAD and defibrillator, resulting in inappropriate defibrillation therapy.
Conclusions: LVADs have a definite impact on cardiac devices in respect with alteration of lead parameters, ventricular tachyarrhythmias, and electromagnetic interference.     

Further flavonol and iridoid glycosides from Ajuga remota aerial parts

Five new iridoid glycosides characterised as 6-keto-8-acetylharpagide (1), 6,7-dehydro-8-acetylharpagide (2), 7,8-dehydroharpagide (3), 8-acetylharpagide-6-O-β-glucoside (4), harpagide-6-O-β-glucoside (5) together with three flavonol glycosides, myricetin 3-O-rutinoside-4'-O-rutinoside (6), myricetin 3-O-rutinoside-3'-O-rutinoside (7) and isorhamnetin 3-O-rutinoside-7-O-rutinoside-4'-O-β-glucoside (8) have been isolated from the aerial parts of Ajuga remota. Also isolated were two known compounds ajugarin IV and ajugarin V. Their structures were established using spectroscopic methods including UV, IR, FAB-MS, HR-MS, 1D and 2D NMR techniques.     

Inhalation Teratology Studies of n-Butyl Mercaptan in Rats and Mice

Inhalation Teratology Studies of n-Butyl Mercaptan in Rats andMice. THOMAS, W. C., SECKAR, J. A., JOHNSON, J. T., ULRICH,C. E., KLONNE, D. R., SCHARDEIN, J. L., AND KIRWIN, C. J. (1987).Fundam. Appl. Toxicol. 8, 170–178. n-Butyl mercaptan (n-BM)is used as a solvent and a chemical intermediate. Pregnant CharlesRiver CD-1 mice and COBS CD rats were randomly assigned to acontrol group and to three n-BM-exposed groups of 25 rats and25 mice each. The animals were exposed by whole-body inhalationto mean n-BM concentrations of 10, 68, or 15 2 ppm on a 6-hrdaily exposure schedule. Rats were exposed on Gestation Days6–19 and mice on Gestation Days 6–16. The controlgroup was exposed to filtered air only on a comparable regimen.Cesarean sections were performed on all surviving mice on GestationDay 17 and on all rats on Gestation Day 20. Seventeen of then-BM-treated mice died: 8 at the 68-ppm level and 9 at the 152-ppmlevel; none of the n-BM-treated rats died. An increased postimplantationloss and increased early resorption occurred in mice exposedat 68 and 152 ppm, indicating embryotoxicity. An increased incidenceof cleft palate was observed in mice exposed to 10 or 68 ppmwhich was not statistically significant. Total fetal abnormalitieswere statistically significantly different from controls at68 ppm where maternal lethality was observed when based on thefetal unit although not when based on the litter unit. Ratsexposed to 152 ppm or less demonstrated no terata.     

Compulsory treatment of substance use disorders

Substance use disorders are the cause of significant suffering for individuals and impose a tremendous burden on society in terms of related social costs. Current drug policy in the USA has failed to have a significant impact on the prevalence or the deleterious effects of this group of illnesses. Crime, violence, family disruption and economic displacement are felt most acutely by already impoverished and disadvantaged communities. The need for a public health approach to these problems rather than a law enforcement solution, is discussed with special attention to compulsory drug use treatment approaches. These approaches are considered in the context of their history and effectiveness through a review of current literature. The positive and negative aspects of compulsory treatment approaches are summarised and recommendations for expanded use of treatment options for clients involved with the criminal justice system are elaborated.     

Inhibition of binding of phospholipase Cγ1 SH2 domains to phosphorylated epidermal growth factor receptor by phosphorylated peptides

A series of tyrosine-containing peptides 1–12: Asp-Ala-Asp-Glu-Tyr⁹⁹²(PO₃H₂)-Leu-Ile-Pro-Gln-Gln-Gly-OH (1) Asp-Ala-Asp-Glu-Tyr⁹⁹² -Leu-Ile-Pro-Gln-Gln-Gly-OH (2) Phe-Leu-Pro-Val-Pro-Glu-Tyr¹⁰⁶⁸(PO₃H₂)-Ile-Asn-Gln-Ser-Val-OH (3) Phe-Leu-Pro-Val-Pro-Glu-Tyr¹⁰⁶⁸ -Ile-Asn-Gln-Ser-Val-OH (4) Asp-Asn-Pro-Asp-Tyr¹¹⁴⁸JR(PO₃H₂)-Gln-Gln-Asp-Phe-Phe-OH (5) Asp-Asn-Pro-Asp-Tyr¹¹⁴⁸ -Gln-Gln-Asp-Phe-Phe-OH (6) Ala-Glu-Tyr¹¹⁷³(PO₃H₂)-Leu-Arg-Val-Ala-Pro-Gln-Ser-OH (7) Ala-Glu-Tyr¹¹⁷³ -Leu-Arg-Val-Ala-Pro-Gln-Ser-OH (8) Ala-Glu-Tyr¹¹⁷³(PO₃H₂)-Leu-Arg-Val-Ala-OH (9) Ala-Glu-Tyr¹¹⁷³ -Leu-Arg-Val-Ala-OH (10) Tyrl¹¹⁷³(PO₃H₂)-Leu-Arg-Val-Ala-Pro-Gln-Ser-OH (11) Tyr¹¹⁷³ -Leu-Arg-Val-Ala-Pro-Gln-Ser-OH (12) (six pairs with and without the tyrosine phosphorylated) has been synthesized. The peptides were derived from tyrosine autophosphorylation sites in the epidermal growth factor receptor (EGFR): Tyr 992, 1068, 1148 and 1173. Peptide 1, derived from the Tyr 992 site, inhibited binding of a ³⁵S-labelled fusion protein containing both of the SH2 domains from PLCγ1 to the phosphorylated EGFR with an IC₅₀ of 8 μM. All of the phosphorylated peptides except 11 (1, 3, 5, 7 and 9) inhibited this binding to some degree (20–55%) at 10 p μM. The nonphosphorylated peptides were inactive in this assay. The nonphosphorylated peptides 2, 4, 6, 8, 10 and 12 were obtained by standard solid-phase synthetic methodologies using both Boc/benzyl and Fmoc/tert-butyl strategies. The phosphorylated peptides 1, 3, 5, 7, 9 and 11 were similarly obtained using a Fmoc/tert-butyl strategy incorporating unprotected N^x-Fmoc-Tyr, followed by phosphitylation and oxidation of the tyrosine in the resin-bound peptide. In addition, Asp-Ala-Asp-Glu-Phe⁹⁹²(4-CH₂PO₃H₂)-Leu-Ile-Pro-Gln-Gln-Gly-OH (15), an analog of 1 incorporating an enzymatically stable phosphotyrosine mimic, 4-phosphonomethyl-l -phenylalanine, was synthesized and found to be inactive.