Increased serum angiotensin-converting enzyme activity and plasma angiotensin II levels during pregnancy and postpartum in the diabetic rat.

OBJECTIVE: The renin-angiotensin system (RAS) plays an important role in the regulation of blood pressure, electrolyte balance and renal function in normal human pregnancy. The present study was designed to assess various components of the RAS and renal function during pregnancy and immediately after pregnancy in the streptozotocin (STZ)-diabetic rat. METHODS: Pregnant Wistar rats were allocated to three groups: I-control, non-diabetic rats (n=24), II-STZ-diabetic rats (STZ 55 mg/kg body weight, i.v. on day 10 of pregnancy, n=24), III-diabetic rats, as above, treated with insulin (4 units/day, s.c. n=21). On days 17-18 of pregnancy, or within 24 hours after delivery, the rats were sacrificed and the various components of the RAS were determined. RESULTS: Urinary protein excretion (UP) and creatinine clearance(CCr) were greater in group II, four days after STZ, than in group I (UP: I-7.6+/-2.8, II-18.6+/-6.3 mg/24-hour, p<0.001, CCr: I-1.04+/-0.33, II-2.38+/-0.7 ml/minute, p<0.001). Mean (+/-SD) serum angiotensin-converting enzyme (ACE) activity and plasma angiotensin II(Ang II) levels at days 17-18 of pregnancy were greater in the untreated diabetic rats than in control pregnant rats (ACE: 163+/-18 vs. 111+/-21 nmol/ml/minute, p<0.001, Ang II: 115+/-45 vs. 43+/-10 pg/ml, p<0.005). Postpartum serum ACE activity and plasma Ang II levels were greater in group II (ACE: I-123+/-14, II-142+/-24, III-108+/-21 nmol/ml/minute, p<0.01, Ang II: I-56+/-38, II-148+/-62, III-38+/-17 pg/mI, p<0.001). ACE activity in the lung was greater, whereas the activity in the renal cortex was less, in group II than in group I. Kidney weight in untreated diabetic rats was greater than in the other two groups. CONCLUSION: Increased serum ACE activity during pregnancy and postpartum in the untreated diabetic rat is associated with enhanced serum Ang II levels, which may contribute to increased protein excretion and renal hypertrophy.

Gastrointestinal anastomosis with the nickel-titanium double ring.

We used a dog model to test the safety and effectiveness of sutureless gastrointestinal anastomoses (n = 23) (end-to-end, end-to-side, or side-to-side) with the nickel-titanium double ring with temperature-dependent shape memory. Results were compared to conventional hand-sutured anastomoses (n = 5). Examination performed after 2 weeks' follow-up showed no leaks and no difference in return of bowel function between the experimental groups and the control group. Microscopic studies showed a complete epithelial lining and perfectly functioning anastomoses. We conclude that the nickel-titanium double-ring device may have an important place in the armamentarium of the gastrointestinal surgeon.

The influence of helium-neon laser irradiation on the viability of skin flaps in the rat.

Low energy helium-neon (He-Ne) laser irradiation has been shown to induce various therapeutic effects. We investigated its effect on the viability of skin flaps in the rat. Thirty rats underwent skin flap elevation and were then divided into three equal groups. Group I (control) was not irradiated. Groups II and III were irradiated for 5 days postoperatively, Group II to the transition zone (between the live and expected necrotic areas) and Group III to the transitional and distal zones; total energy, 2.9 J/cm(2)for each rat. Ten days after the last treatment larger surviving areas were demonstrated macroscopically in Groups II and III (P< 0.01 and 0.001, respectively). Histological examination showed tremendous proliferation of capillaries (P

Cyclic AMP decreases the availability of 5-phosphoribosyl-1-pyrophosphate and decelerates de novo purine synthesis in rat hepatocytes.

Cyclic adenosine monophosphate (cAMP) was found to decrease the availability of 5-phosphoribosyl-1-pyrophosphate (PRPP) and to decelerate the rate of de novo purine synthesis in suspensions of adult rat hepatocytes. Glucagon did not affect these parameters. The glucagon antagonist des-His1[Glu9]glucagon amide (DHGA), and the protein kinase C activator 1,2-dioctanoyl-sn-glycerol (DOG) were also found to lower PRPP availability. Incubation of the hepatocytes with dbcAMP or with DHGA, did not alter the activity of PRPP synthetase in the hepatocyte lysates, indicating that the above effects are not mediated through the activity of this enzyme. The possibility that the decrease in PRPP availability reflects increased consumption associated with accelerated pyrimidine synthesis is discussed. The decelerated rate of de novo purine synthesis is probably secondary to the decreased PRPP availability.

Insulin treatment reduces the increased serum and lung angiotensin converting enzyme activity in streptozotocin-induced diabetic rats.

Serum and lung angiotensin-converting enzyme (ACE) activity is increased in the streptozotocin (STZ)-diabetic rat. In the present study, the effect of insulin treatment on this increased ACE activity in the STZ-diabetic rat was investigated. Serum and tissue ACE activity was determined by radiometric assay using [3H]-Hippuryl-glycyl-glycine as substrate. Fifteen days after onset of diabetes (n = 16), 8 rats received insulin daily (6-12 units/kg, s.c.) for 33 days, 8 diabetes rats remained untreated. Control, non-diabetic, rats (n = 8) received saline. The baseline serum ACE activity in the control group was 595 +/- 13 nmol/ml/min and did not change significantly throughout the study. However, serum ACE activity in the untreated diabetic rats increased significantly as of day 14 post-STZ (650 +/- 24 nmol/ml/min, p < 0.001) compared to the corresponding values of the control group and compared to baseline values. Insulin administration to diabetic rats starting on day 15 post-STZ caused a gradual reduction in serum ACE activity to basal values, being (527 +/- 22 nmol/ml/min) at day 47. ACE activity in lungs of untreated diabetic rats was increased by 46%, 47 days post-STZ. Insulin treatment reduced lung ACE activity to values similar to those observed in non-diabetic rats. These changes were associated with reduced kidney weight and urine volume. In summary, insulin administration to hyperglycaemic rats resulted in a reduction in the enhanced serum and lung ACE activity to values seen in non-diabetic rats. Normalizing the activity of the renin-angiotensin system may slow or prevent the glomerular hypertension, a major factor in the development of diabetic nephropathy.

Fiberoptic-guided CO2 laser for harvesting of the internal mammary artery.

OBJECTIVE: The internal mammary artery is the preferred conduit in coronary artery bypass grafting. Although most centers use electrocautery to dissect the internal mammary artery, it has several disadvantages. The purpose of this study in a canine model was to evaluate and compare a fiberoptic CO2 laser device versus electrocautery for harvesting the internal mammary artery. MATERIAL AND METHODS: In ten mongrel dogs, both internal mammary arteries with their surrounding pedicles, were dissected from the thoracic wall, using a low-current electrocautery for one artery and a continuous wave, fiberoptic-guided CO2 laser (13 watts) for the contralateral vessel. Blood flow through the vessels was measured immediately after dissection. RESULTS: Mean flow through the laser dissected arteries was 71.3 +/- 23.7 ml/min versus 52.9 +/- 16.5 ml/min in those dissected using electrocautery. Histological examination of the chest wall specimens dissected with electrocautery showed the presence of necrosis, edema and hemorrhage surrounding the muscle, while the specimens dissected with the laser revealed only a narrow area of burn on the surgical margins of the muscle. The laser-assisted dissection was more accurate, as easy, and almost as fast as with the use of electrocautery. CONCLUSIONS: Stripping of the internal mammary artery with the fiberoptic CO2 laser offers a promising alternative to electrocautery. Owing to its greater accuracy, the laser technique may reduce the likelihood of damaging the endothelial lining of the dissected vessel. By reducing the degree of soft tissue damage, the CO2 laser may also lower the incidence of sternal wound infection and reduce postoperative chest wall pain and dysesthesia.

Treatment of experimental inflammatory synovitis with continuous magnetic field.

The effect of a magnetic field on synovitis in rats was studied. Synovitis was induced by bilateral intraarticular injection of zymosan to the hind joints. One group of rats was held in a cage with a magnet of 3,800 Gauss on the bottom of the cage (treated), while another group was held in a cage without a magnet (control). Three weeks following intraarticular zymosan injection all rats were killed and the hind joints tissues were examined histologically. The pathologic process was noted and graded according to the involvement of various tissue components, number of inflammatory foci, and size of the lesion. The histologic findings of the tissues from the control group consisted of marked articular infiltrate, composed of lymphocytes and plasma cells with some histocytes in 80% of the animals. A small articular infiltration of the same nature was observed in 20% of the treated rats. The inflammatory score was 3.4 +/- 1.1 in the treated animals and 6.8 +/- 2.6 in the control group (P = 0.002). These data showed that synovitis and the inflammatory process are significantly suppressed by a magnetic field.

Effect of green argon (514 nm) laser exposure on rose bengal-stained guinea pig cornea.

Our purpose was to study the effect of continuous wave (CW) green argon laser (514 nm) exposure on rose bengal-stained cornea. Following staining with rose bengal (1%), the corneas of 48 albino guinea pigs were exposed to different power levels of argon laser, ranging between 0.04 and 0.8 W. The beam diameter ranged between 50 and 200 microns, and exposure time was 0.1 sec. Histology revealed minimal tissue coagulation at 0.05 W and 50 microns. Moderate coagulation of the anterior stromal lamellae was found at power levels of 0.07-0.6 W and a beam diameter of 100-200 microns. At power levels of 0.7 and 0.8 W, lamellar disruption was also noted. Our data indicate that 1% rose bengal is a good photosensitizer for superficial corneal stromal photocoagulation.

The CO2 laser in the treatment of lesions of the eyelids and periorbital region.

The CO2 laser can be used for the treatment of various lesions of the eyelids and peri-orbital region with the advantage over other modalities of precise, controllable, hemostatic, non contact atraumatic ablation with the reduction of post-operative pain and improved cosmetic results. Its application in palpabral and peri-orbital surgery is recommended.

Successful treatment of anal tumors with CO2 laser in elderly, high-risk patients.

The central issue in elderly surgery remains the operative risk, which is usually a direct factor of age, ASA classification, and other pathologies, especially cardiovascular diseases. It is the surgeon's role to define properly the risks involved with a patient and to anticipate the involved operative mortality. Based on this, we performed CO2 laser fulguration of anal canal tumors in 10 patients suffering from either squamous cell or adenocarcinoma localized up to 4 cm from the anus. The rationale was to avoid prohibitive operative and anesthetic risk, achieve local control of disease and improve quality of life by avoiding surgical convalescence and an otherwise certain colostomy. All patients underwent fulguration (25-30 W) every 3-4 months. Complications included minor pain and bleeding. Three patients required operation (Hartman's pouch) within 2 1/2 years due to continuous tumor bleeding and stricture of the anal canal. The remaining 7 patients were treated regularly and satisfactorily by fulguration and the mean survival in this group was 8 years (in all cases the causes of death were unrelated to the procedure or the tumor). We conclude that CO2 laser fulguration of anal canal tumors in elderly, high-risk patients represents an invaluable option of treatment, while avoiding major operative risk, controlling the local spread of disease, maintaining physiological bowel function, and avoiding colostomy. Most importantly, the main dividends of the study are patient satisfaction and maintenance of good quality of life.

Use of Vicryl mesh to support the esophageal wall after circular myotomy (Livaditis procedure) in long-gap esophageal atresia - an experimental study.

Circular esophageal myotomy (CEM) is currently a well-accepted technique for elongation of the upper esophageal pouch in cases of long-gap esophageal atresia (EA). Esophageal pseudodiverticulum is a frequent and perhaps underreported sequela of this technique, characterized by ballooning or outpouching of the esophageal mucosa in the myotomized area. The present study was designed to seek a supplement for the CEM technique in order to avoid possible pseudodiverticulum formation in the myotomized area. We created an animal model to simulate the anatomic conditions present after primary repair of EA facilitated by CEM. Three groups of dogs underwent either cervical (1 group) or thoracic (2 groups) esophageal myectomy. In the cervical and first thoracic groups, the denuded mucosa was left without any support. In the second thoracic group, the denuded mucosal area was wrapped with polyglactin 910 (Vicryl) mesh. In all three groups the esophagus was narrowed by a Marlex mesh ring 3 cm distal to the myectomized zone, simulating a condition resulting from anastomotic narrowing. The dogs underwent barium swallows under fluoroscopy at different postoperative periods and were killed 4 or 6 months after surgery. The esophagi were removed for gross and radiologic investigation under maximal insufflation as well as for histologic assessment. The proposed canine model proved to be useful for study of the myectomized esophagus, mimicking the anatomy and conditions after CEM in long-gap EA repair. Wrapping the denuded mucosa with Vicryl mesh fortified the weakened esophageal wall, thus diminishing the likelihood of future pseudodiverticulum development. In light of the simplicity of the technique and the absence of any evident risk or complications, we recommend that the use of Vicryl mesh wrap be considered during CEM to reinforce the esophageal wall.

The use of CO2 laser for inguinal hernia repair in elderly, pacemaker wearers.

Interference of electrical current with pacemaker activity is well known and has long been described. Almost every surgical procedure is now performed with the electrical knife, or electrocautery. In patients wearing a pacemaker this poses a problem, because of the danger of electronic interference within the pacemaker with consequent firing-frequency changes and the higher risk of intra- and postoperative bleeding and oozing when using a scalpel instead of cautery. We have performed 25 hernioplasties in elderly patients with permanent pacemakers using the CO2 laser technique. All operations were technically successful, and the immediate and long term (1 year) follow-up proved uneventful. Additionally normal pacemaker function was maintained during surgery and through the follow-up period. CO2 laser surgery is advantageous over electrocautery in patients with pacemakers because it does not interfere with pacemaker activity. Moreover, the laser produces normal hemostasis and does not stimulate muscle and nerve activity during surgery.

Clomiphene citrate reduces procarbazine-induced sterility in a rat model.

Chemotherapy with the cytotoxic drug procarbazine (PCB) causes permanent infertility in most male patients. Since many patients treated with this cytotoxic drug are of reproductive age, it is important to develop a method to protect spermatogenesis and fertility. It has been hypothesised that 'spermatogenic arrest' by pharmacological intervention may render the testes less susceptible to the effects of chemotherapy. The present study investigated whether recovery of fertility in a male rat model could be achieved by suppression of spermatogenesis with high doses of clomiphene citrate (CC) prior to PCB administration. It was demonstrated that young male rats treated with a combination of CC and PCB partially recovered spermatogenesis and achieved almost normal fertility. In contrast, animals treated with PCB alone exhibited abnormal spermatogenesis and remained infertile.

The CO 2 laser in mastectomy: a ten-year follow-up.

We compared the healing process, postoperative course, and follow-up of patients who underwent modified radical mastectomy in the conventional way with those who underwent a laser procedure. Sixty women, aged 33 to 77 years, who suffered from carcinoma of the breast were randomly divided into two groups: Group 1: surgery was performed using scalpel and electrosurgery; Group 2: surgery was performed with a CO 2 Sharplan laser, skin-to-skin including the axilla dissection; maximal power, 40-60 W. The postoperative course was uneventful in both groups. Wound healing was normal. Sutures were removed on the tenth day. Patients were followed at the Outpatient Clinic for 10 years. The circumference of the arm and forearm was measured at fixed points before surgery and at follow-up. Mammography and liver and bone scans were performed every year. Four Group 1 patients developed swelling and edema of 2 to 3 cm at 6 to 8 months after surgery. Also two patients from subgroup A developed local recurrence. No edema or swelling or local recurrence could be detected in patients operated by laser. Surgery with laser is preferable to the conventional approach.

Increased leukocyte adhesiveness/aggregation and tissue leukostasis following surgical trauma.

The purpose of the present study was to document the increased leukocyte adhesiveness/aggregation (LAA) and tissue leukostasis that follow surgical trauma. We found that following major abdominal surgery, the percentage of aggregated leukocytes in the peripheral blood increased from 8.6 +/- 7 to 21.7 +/- 11.5 (p < 0.001), while the respective values for patients undergoing minor surgery were 3.7 +/- 2.4 and 19.7 +/- 7.6% (p < 0.001). The state of LAA was also determined in eight dogs after partial collectomy and four controls. A clear increment in the degree of tissue leukostasis (especially in the spleen, liver and lungs) was noted in the operated as compared to the control animals. In addition, a significant correlation was found between the state of LAA, determined in the venous (p = 0.0004) and arterial (p = 0.002) blood of these animals and the degree of tissue leukostasis. We conclude that a state of increased LAA in the peripheral blood is induced by surgical trauma and that this increased LAA correlates with tissue leukostasis.

Experimental surgery on dog's stomach and liver using CO 2 laser plastic hollow fibers: technical method.

Plastic hollow fibers for the transmission of CO 2 laser energy in curved paths were produced by plating the inner surface of plastic tubes with a metal film and dielectric film upon it. These fibers can transmit high power up to 40 W at the outlet, with high transmission yield even through several bendings. A three-dimensional simulator was built to simulate paths in the dog's body and the outlet power was measured. From the achieved data the expected transmitted power during real surgery was appreciated. The fibers were checked for their influence on live tissues of dogs. Incisions were made in the liver and ulcers in the dogs' stomachs were treated. The fibers were inserted into the stomach through the dogs' esophagus. Complete healing was observed after four weeks.

The effect of local deep microwave hyperthermia on experimental zymosan-induced arthritis in rabbits.

The effect of local deep microwave hyperthermia (LDMWH) on normal and Zymosan-induced arthritis has been evaluated in 12 rabbits (24 joints). LDMWH, four treatments to each joint (twice weekly for a period of 2 wk), was generated by an antenna operating at 915 MHz for 60 min, reaching an intraarticular temperature of 42.5 +/- 0.5 degrees C. A surface cooling system was used with the microwave apparatus. Two weeks after the last treatment, all animals were sacrificed. The application of LDMWH on normal joints induced a limited proliferation of the synovial lining cells with a minimal perivascular infiltration of mononuclear and neutrophil cells. However, no histologic damage to the skin, muscles, bone, cartilage or bone marrow adjacent to the heated joints could be noted. Induction of Zymosan arthritis (2 wk before LDMWH) was characterized by pannus formation and granulomatous reaction accompanied by fibrinoid deposits and disseminated necrotic foci in the synovial intima. The LDMWH treatment on the examined arthritic joints brought about a reduction in the degree of granulomatous reaction concomitant with the appearance of some fibrocytes and fine collagen fibrils. These findings suggest that LDMWH can be safely applied, even repeatedly, without morphologic evidence of damage to any normal mesenchymal tissue. Moreover, it reduces the inflammatory process in experimentally induced synovitis.

Preliminary experiments of possible uses in medicine of novel plastic hollow fibers for transmission of CO2 radiation.

Plastic hollow fibers for the transmission of CO2 laser energy in curved paths were produced by plating the inner surface of plastic tubes with a metal film and dielectric film upon that. These fibers can transmit high power, up to 40 W at the outlet, with high transmission yield even through several bendings. To demonstrate a possible use of the fibers, they were checked for their influence on live tissues of dogs. Incisions were made in the liver, and ulcers in the dogs' stomachs were treated. The fibers were inserted into the stomach through the esophagus. Complete healing was observed after 4 weeks.

Transcutaneous electrical stimulation of the normal rabbit joint.

To determine the effect of transcutaneous electrical stimulation on the rabbit joint, we studied skin and intraarticular temperatures and pressure both before and following the stimulation in nine rabbits. An elevation in skin temperature by a mean of 0.6 degrees C (p less than 0.05) and increase in intraarticular temperature by a mean of 0.8 degrees C (p less than 0.01) was noted following the electrical stimulation. Intraarticular pressure in the stimulated joints has only a trend to increase, but not significantly. In four other rabbits, synovial tissue of the stimulated joint showed blood vessels congestion and interstitial edema. These results suggest that the analgetic effect produced by electrical stimulation on joints may partially involve intraarticular temperature and pressure alterations.