The S631A mutation causes a mechanistic switch in the block of hERG channels by CnErg1.

We have studied the interaction of CnErg1, a member of the gamma-KTX subfamily of scorpion toxins with the inactivation-deficient S631A hERG channel. In the background of this mutation, we observed a mechanistic switch from turret block, characteristic of the action of gamma-KTXs on Kv11-type channels, to pore plugging, characteristic of alpha-KTX block of Kv1-type channels. We suggest this reflects destabilization of the outer pore (turret region) of hERG allowing access of the toxin molecule to directly plug the conduction pathway.

Characterization and isolation of L-to-D-amino-acid-residue isomerase from platypus venom.

Platypus venom contains an isomerase that reversibly interconverts the second amino-acid residue in some peptides between the L-form and the D-form. The enzyme acts on the natriuretic peptides OvCNPa and OvCNPb, and on the defensin-like peptides DLP-2 and DLP-4, but it does not act on DLP-1. While the isomerization of DLP-2 to DLP-4 is inhibited by the amino-peptidase inhibitor amastatin, it is not affected by the leucine amino-peptidase inhibitor bestatin. The enzyme, that is only present in minute quantities in an extract of the venom gland, is thermally stable up to 55 degrees C, and it was found by anion-exchange chromatography to be acidic. Isolation of the isomerase was carried out by combined ion-exchange chromatography and reverse-phase high performance liquid chromatography (HPLC).

A preliminary study on the effect of ultrasound therapy on the healing of surgically severed achilles tendons in five dogs.

This study was conducted on the left Achilles tendon in five clinically normal dogs. The Achilles tendon was surgically exposed and severed 3-4 cm proximal to the point of its insertion. Tenorrhaphy was undertaken by the application of three sutures on the various tendon units of the Achilles tendon using single locking-loop sutures with polyamide no. 1-0. The superficial digital flexor tendon was sutured with catgut using two horizontal mattress sutures. No ultrasound therapy was used in the animals of group I (control). Ultrasound therapy was given to the animals of group II (treated) starting from the third day post-operatively at 0.5 W/cm2 for 10 min daily for 10 days. A cortical screw was used for immobilization of the tibiotarsal joint which was removed 4 weeks after tenorrhaphy. Post-operatively, healing of the Achilles tendon was monitored using clinical observations, ultrasonography, gross and histomorphological observations at various intervals up to 120 days in both groups. Clinically, the dogs showed significant lameness for the first 4-5 days, which disappeared earlier in the ultrasound-treated (group II) animals than the controls (group I). Extension and flexion of the hock joint were found to be near normal at 6 weeks after the repair of the Achilles tendon. Ultrasonography showed anechoic to hypo-echoic echo-texture on days 3 and 7 after repair. By day 40, the echo-texture started to improve to hypo-echoic in group II, but in group I anechoic areas were still observed. However, the tendon showed near normal mottled hypo- to hyper-echoic texture in both groups by day 120. Gross observations suggested that the Achilles tendon in group II showed comparatively fewer adhesions than in group I animals. Histologically, in group II (treated), on day 40, the union was comparatively better without any inflammatory reaction. Bundle formation had begun in the ultrasound-treated animals which was not observed in the control animals. By day 90, more compact parallel bundle formation had taken place with minimum cellularity. Bundle formation was in its advanced stage in the treated animals. By day 120, the tendon tissue was comparatively acellular and looking like a normal tendon. The use of the cortical screw provided good immobilization and ultrasound therapy at 0.5 W/cm2 enhanced the Achilles tendon healing in dogs.

Histomorphochemical effects of shortwave diathermy on healing of experimental muscular injury in dogs.

The biceps femoris muscle was surgically incised and sutured in 10 clinically healthy mongrel dogs, aged 1-2 yr and weighing 10-15 kg. The surgical wounds of 5 dogs were exposed to shortwave diathermy for 5 min daily for 7 days, starting a day after the creation of trauma. The remaining 5 dogs served as control. After 15 days of healing, the tissues from biceps femoris muscle were collected and subjected to histomorphological and histochemical examination. Mature collagen bundles were seen at healing site in diathermy treated animals while there were immature collagen fibres and more number of fibroblasts in control animals. Normal muscle fibres could be seen on either side of the healing tissue in treated animals whereas in control animals, atrophied and necrosed muscle fibres were encountered. The neutral and acid mucopolysaccharides, lipid droplets in the intermyofibrillar area and the activity of alkaline phosphatase, adenosine triphosphatase and lactate dehydrogenase at the healing site was better in treated as compared to controls.

Haloperidol as a pre-medicant for thiopental anaesthesia in the dog.

Haloperidol was administered intravenously at the dose rate of 0.87 mg/kg body weight five minutes prior to thiopental anaesthesia in 5 clinically healthy dogs, aged 10-12 months and weighing 11.5 +/- 0.96 kg. Animals required only 4.36 +/- 0.24 ml of the 5% thiopental sodium to achieve surgical anaesthesia which lasted for 37.5 +/- 4.3 minutes. There was adequate muscle relaxation and loss of pedal and palpebral reflexes during thiopental anaesthesia. Five minutes after administration of haloperidol, there was no appreciable change in the various cardiopulmonary dynamics with the exception of a hypocapnoea and a mild hypotension. During thiopentone anaesthesia, a mild hypotension and arterial hypoxemia was evident. This combination of anaesthesia was also employed in 14 clinical cases varying from fractures of long bones (4), mammary tumours (3), ear haematoma (4), venereal granuloma (2) and abdominal hernia (1). The combination proved extremely useful for orthopaedic surgery as the muscle relaxation was adequate and the reduction of the fractured ends was relatively easy.

Studies on lorazepam as a premedicant for thiopental anaesthesia in the dog.

Four mg of lorazepam was given intravenously 5 min prior to thiopental anaesthesia in 5 clinically healthy dogs weighing 14 +/- 2 kg and aged about 10-12 months. Animals required only 7.0 +/- 1.5 ml of 5% thiopental sodium to achieve surgical anaesthesia which lasted about 30.4 +/- 3.3 minutes. There was adequate muscle relaxation and loss of pedal and palpebral reflexes. Five min after administration of lorazepam, there was no appreciable change in various cardiopulmonary dynamics. However, there was moderate arterial hypertension, tachycardia and arterial hypoxemia 15 min after the onset of the thiopental anaesthesia. There was no respiratory depression. The lorazepam-thiopental combination was also attempted in 16 clinical cases varying from repair of fractures of long bones (9), mammary tumour (2), ear haematoma (1), ear cropping (1), tail gangrene (2) and rectal prolapse (1). This combination of anaesthesia proved extremely useful for orthopaedic surgery as the muscle relaxation was adequate and reduction of the fractured ends was comparatively easier.