Sinomenine, an Alkaloid Derived from Sinomenium acutum Potentiates Pentobarbital-Induced Sleep Behaviors and Non-Rapid Eye Movement (NREM) Sleep in Rodents

Sinomenium acutum has been long used in the preparations of traditional medicine in Japan, China and Korea for the treatment of various disorders including rheumatism, fever, pulmonary diseases and mood disorders. Recently, it was reported that Sinomenium acutum, has sedative and anxiolytic effects mediated by GABA-ergic systems. These experiments were performed to investigate whether sinomenine (SIN), an alkaloid derived from Sinomenium acutum enhances pentobarbital-induced sleep via γ-aminobutyric acid (GABA)-ergic systems, and modulates sleep architecture in mice. Oral administration of SIN (40 mg/kg) markedly reduced spontaneous locomotor activity, similar to diazepam (a benzodiazepine agonist) in mice. SIN shortened sleep latency, and increased total sleep time in a dose-dependent manner when co-administrated with pentobarbital (42 mg/kg, i.p.). SIN also increased the number of sleeping mice and total sleep time by concomitant administration with the sub-hypnotic dosage of pentobarbital (28 mg/kg, i.p.). SIN reduced the number of sleep-wake cycles, and increased total sleep time and non-rapid eye movement (NREM) sleep. In addition, SIN also increased chloride influx in the primary cultured hypothalamic neuronal cells. Furthermore, protein overexpression of glutamic acid decarboxylase (GAD(65/67)) and GABA(A) receptor subunits by western blot were found, being activated by SIN. In conclusion, SIN augments pentobarbital-induced sleeping behaviors through GABA(A)-ergic systems, and increased NREM sleep. It could be a candidate for the treatment of insomnia.

Rhynchophylline, One of Major Constituents of Uncariae Ramulus et Uncus Enhances Pentobarbital-induced Sleep Behaviors and Rapid Eye Movement Sleep in Rodents

Rhynchophylline (RP) is a major tetracyclic oxindole alkaloid of Uncariae Ramulus et Uncus which has been used to treat hypertension, seizures, pain and anxiety in the oriental countries. A recent report revealed that RP attenuated ischemia-induced neuronal damage and kainite-induced convulsions in animals. This study was performed to investigate whether RP enhances pentobarbital-induced sleep behaviors and modulates sleep architecture in mice. Locomotor activity was significantly inhibited by RP at 0.25 and 0.5 mg/kg, similar to 2 mg/kg diazepam (a benzodiazepine agonist) in mice. RP shortened sleep latency and increased total sleep time in a dose-dependent manner when administrated with pentobarbital (42 mg/kg, i.p.). RP also increased the number of sleeping mice and total sleep time by concomitant administration with the sub-hypnotic dosage of pentobarbital (28mg/kg, i.p.). On the other hand, RP (0.25mg/kg, p.o.) itself significantly inhibited sleep-wake cycles, prolonged total sleep time, and rapid eye movement in rats. In addition, RP also increased chloride influx in the primary cultured hypothalamic neuronal cells. In addition, we found that glutamic acid decarboxylase (GAD(65/67)) was activated by RP. In conclusion, RP augments pentobarbital-induced sleeping behaviors, and can be a candidate for treating insomnia.

4-Hydroxybenzaldehyde, One of Constituents from Gastrodiae Rhizoma Augments Pentobarbital-induced Sleeping Behaviors and Non-rapid Eye Movement (NREM) Sleep in Rodents

In the previous experiments, we reported that ethanol extract of Gastrodiae Rhizoma, the dried tuber of Gastrodia ElataBlume (Orchidaceae) increased pentobarbital-induced sleeping behaviors. These experiments were undertaken to know whether 4-hydroxybenzaldehyde (4-HBD), is one of the major compounds of Gastrodiae Rhizoma increases pentobarbital-induced sleeping behaviors and changes sleep architectures via activating GABA(A)-ergic systems in rodents. 4-HBD decreased locomotor activity in mice. 4-HBD increased total sleep time, and decreased of sleep onset by pentobarbital (28 mg/kg and 40 mg/kg). 4-HBD showed synergistic effects with muscimol (a GABA(A) receptor agonist), shortening sleep onset and enhancing sleep time on pentobarbital-induced sleeping behaviors. On the other hand, 4-HBD (200 mg/kg, p.o.) itself significantly inhibited the counts of sleep-wake cycles, and prolonged total sleep time and non-rapid eye movement (NREM) in rats. Moreover, 4-HBD increased intracellular Cl- levels in the primary cultured cerebellar cells. The protein levels of glutamic acid decarboxylase (GAD) and GABA(A) receptors subunits were over-expressed by 4-HBD. Consequently, these results demonstrate that 4-HBD increased NREM sleep as well as sleeping behaviors via the activation of GABA(A)-ergic systems in rodents.

Reconstruction of median sternotomy dehiscence

Complications after a median sternotomy incision, which is used currently in most open heart surgery, are serious, although it is infrequent. Reconstruction of the sternal defect resulting from dehiscence of median sternotomy is still big challenge to the most plastic surgeons. Since vascularized greater omentum was transposed to eliminate mediastinal wound problems, many vascularized regional muscle flaps became mainstay in reconstruction of median sternotomy wound. We treated 13 patients with median sternotomy dehiscence between October of 1993 and March of 1998. In two patients, the wound problems were so confined to superficial tissue that debrided and closed primarily. Eleven patients with deep wound infection were managed with vigorous debridement of all necrotic tissues and resultant defects were covered with regional muscle flaps: rectus myocutaneous flap(3) and bilateral pectoralis advancement flap(8). We used the pectoralis major advancement flaps without counter incision at humeral insertion site and the dissections were limited only medial to the anterior axillary line to preserve the axillary fold. In five patients with larger defects, we elevated muscle and cutaneous flaps separately to make these flaps more mobile. Large portion of two rectus abdominis flaps could not survive, whereas pectoralis advancement flaps had mo special wound problems. Only one patient developed fistula due to remained wire, regardless to flap surgery.