In the cut and thrust of apoptosis, serine proteases come of age

Proteolysis is central to the systematic cellular degradation that occurs during apoptosis. Predominantly, caspases have been studied in this regard. However, increasing evidence suggests that certain serine proteases may also play a significant role in apoptosis. Not only are these serine proteases involved in apoptosis signalling pathways independently, but they may also interact with more classical mediators of apoptosis such as the caspases or Bcl-2 family proteins. Isolation of apoptosis-associated serine proteases and the use of specific inhibitors have helped to shed light on potential pathways in which they are involved. Despite the recent developments in the field, knowledge regarding the role of serine proteases in apoptosis remains limited, but it is clear that investigations are gathering momentum and such studies may herald a new and exciting departure in apoptosis research.     

Adrenoceptor mechanisms underlying imipramine-induced memory deficits in rats

The post-training administration of tricyclic antidepressant imipramine impairs memory consolidation in the passive avoidance task. The present study investigated the effects of intrahippocampal (i.h.) injection of adrenoceptor agents on imipramine-induced (2-8 microg/rat) amnesia. The administration of the alpha1-adrenoceptor agonist phenylephrine (0.05 microg/rat) and the alpha1-adrenceptor antagonist prazosin (0.5 microg/rat) did not alter the effect of imipramine. The lower doses of phenylephrine (0.005 and 0.015 microg/rat) impaired, while the higher dose of the drug (0.025 and 0.05 microg/rat) improved retention. The effect of phenylephrine was not altered by prazosin (0.5 and 1 microg/rat) pretreatment, although prazosin alone decreased retention latencies. The alpha2-adrenoceptor antagonist yohimbine (0.5 and 1 microg/rat) decreased the response induced by imipramine. However, the alpha2-adrenoceptor agonist clonidine (0.08 microg/rat) did not alter the effect of the drug. Clonidine (0.15 and 0.3 microg/rat) by itself decreased, while yohimbine (1 and 2 microg/rat) increased retention latencies. Yohimbine pretreatment attenuated the effect of clonidine. It is concluded that alpha2-adrenoceptor mechanism(s) may be involved in imipramine-induced impairment of memory.     

Hydro-Jet-assisted laparoscopic cholecystectomy: a prospective randomized clinical study

BACKGROUND: A new dissection technique with high-pressure water stream (Hydro-Jet) has recently been applied for selective dissection during various surgical procedures. The aim of this study was to compare Hydro-Jet with the conventional technique for laparoscopic cholecystectomy. METHODS: Eighty patients were randomized to undergo laparoscopic cholecystectomy with standard (n = 40) or Hydro-Jet-assisted (n = 40) dissection techniques. The rates of intraoperative complications, including blood loss and injury to the adjacent organs, were compared between the groups. The versatility of this technique and the features of surgical dissection were also evaluated and compared. RESULTS: Laparoscopic cholecystectomy was successfully completed in all subjects. The mean operative times were 78 minutes (range, 52-120 minutes) and 81 minutes (range, 45-135 minutes) for Hydro-Jet versus conventional dissection, respectively (P = not significant). Complications included gallbladder perforation in 15% and 30% (P <.1) and liver laceration in 0% and 10% (P <.04) with Hydro-Jet and conventional techniques, respectively. Increased hemorrhage from the gallbladder bed that necessitated fulguration occurred in 12 patients with the conventional technique as compared with none in the Hydro-Jet group (P <.001). Hydro-Jet resulted in a selective dissection of connective tissue preserving blood vessels and the cystic duct. The continuous water flow allowed a clear view for the operator, and the dissection was performed in a relatively bloodless field. The ease of blunt dissection with the bent-tip dissector represents another advantage. CONCLUSION: This study shows that Hydro-Jet dissection represents an excellent alternative to the conventional technique for laparoscopic cholecystectomy. The improved anatomic dissection combined with an almost bloodless operating field as the result of continuous water flow decreased the rate of dissection-related complications.     

Pancreatitis after liver transplantation in children: a single-center experience

BACKGROUND AND METHOD: Posttransplantation acute pancreatitis (PTAP) is a rare but serious complication after pediatric liver transplantation (LTx). We performed a retrospective review in a large cohort of pediatric liver transplant recipients at a single institution to define the impact of this problem in children. RESULTS: Between January 1986 and December 1999, 634 pediatric LTx were performed. Twenty-six patients developed serious acute pancreatitis. The mean age at transplantation was 7.7 years (9 months to 19 years), and the indications for transplantation were biliary atresia in seven, fulminant hepatic failure in six, chronic rejection in seven, and other etiologies in six patients. PTAP was more likely to occur early after LTx (61% within the first week), was associated with the presence of an infrarenal aortic graft in 14 (54%) of 26 patients, was more likely to occur after retransplantation (11/26 patients), and was associated with blood loss and prolonged surgery in four cases. Acute renal failure occurred in 15 (58%) of 26 patients. Mortality was 42% (11/26); causes of death were sepsis or multiple organ failure in nine and hemorrhage in two patients. Management of PTAP included antibiotics, sphincterotomy, debridement with drainage, hepatic arterial revascularization, and arterial ligation. Of the 14 patients with complicated pancreatitis, 5 were treated conservatively and died. Nine patients had extensive operative interventions and four survived (45%). CONCLUSIONS: Several risk factors such as retransplantation, extensive dissection at the time of LTx, and use of infrarenal arterial graft contribute to development of PTAP in children. Early exploration and debridement in patients with complicated pancreatitis may result in a better outcome. Retransplantation in the presence of clinical pancreatitis has a high failure rate.     

Pregnancy after liver transplantation with tacrolimus immunosuppression: a single center's experience update at 13 years

BACKGROUND: Chronic liver disease often leads to amenorrhea in women of childbearing age. There are several reports of successful pregnancy after liver transplantation (LTx) with cyclosporine A immunosuppression. Tacrolimus has been increasingly used in solid-organ transplantation, and the effect of the drug on pregnancy is still of interest to clinicians. This study updates our single-center experience. METHODS: All pregnancies after LTx with tacrolimus immunosuppression were followed prospectively. Patients' clinical courses during pregnancy and labor along with gestational period and birth weight were catalogued. Changes in liver function, renal function, and immunosuppression also were recorded. The birth weight percentile was calculated on the basis of the gestational period using a standard chart. RESULTS: Thirty-seven mothers delivered 49 babies. Three mothers delivered three times, and six mothers delivered two times. Thirty-six mothers (97%) survived the pregnancy, and 36 allografts (97%) survived. The one death and graft loss was in a patient who demonstrated infra-aortic arterial graft, which clotted by the gravid uterus during labor. The patient developed a gangrenous liver and died before she could undergo retransplantation. The mean gestational period was 36.4+/-3.2 weeks, excluding two premature deliveries at 23 and 24 weeks gestation. Twenty-two babies (46.9%) were delivered by cesarean section, and the other babies were delivered vaginally. In addition to the two premature babies, one baby, who was born to a mother with Alagille syndrome, died from congenital birth defects. The rest of the newborns survived. The mean birth weight was 2,797+/-775 g, with 38 babies (78%) weighing more than 2,000 g. The mean birth weight percentile to gestational period was 54+/-23. Four babies (8.5%) had a birth weight percentile of less than 25, and 28 babies (59.6%) had a birth weight percentile greater than 50. Twelve patients demonstrated an increase in hepatic enzymes without jaundice during the pregnancy. All of them responded to augmentation of immunosuppression. CONCLUSION: The present report reconfirms the safety of tacrolimus during pregnancy after LTx. Preterm delivery and low birth weight seem to be a persistent problem in all solid-organ transplantation under any form of immunosuppression. However, toxemia of pregnancy and new onset of hypertension seem to be have a low occurrence with the use of tacrolimus.     

Orbicularis oculi muscle stripping and tarsal fixation for recurrent entropion

This prospective study highlights the result of a new technique for correction of recurrent lower lid entropion. The technique was designed to address the aetiological factors involved based on the pre- and per-operative findings. MATERIAL AND METHODS. 37 eyelids of 31 consecutive patients with recurrent entropion were enrolled. Under local anaesthesia, a horizontal incision was made at the lower border of the tarsus, involving the total width of the lower eyelid. Anterior lamellar (skin and orbicularis oculi muscle - OOM) inferior to the incision was dissected towards the orbital rim. An ellipse of the excess overriding OOM and overlying skin inferior to the incision was excised. The OOM was fixed to the lower border of the tarsus with three to four 6/0 Vicryl subcutaneous sutures. Skin was repaired with 6/0 silk sutures, which were removed five days post-operatively. Five cases underwent horizontal lid shortening and 15 had preaponeurosis fat sculpting in addition. RESULTS. 37 procedures were performed on 31 patients (23 M & 8 F). The mean age was 76.5 yrs. (range 63-90). The patients had had one to four (mean = 1.7) previous surgeries. All patients had OOM override. Fifteen had significant preaponeurosis fat prolapse. Lower lid laxity was not identified in all cases, in some due to previous lid surgery. There was no evidence of lower lid retractor laxity in the majority of cases. After a mean follow-up time of 18 months (5-36) there were three recurrences. One underwent further tarsal fixation and the other two had horizontal lid shortening with a favourable outcome. CONCLUSIONS. Excision of overriding OOM and tarsal fixation for recurrent entropion is simple and effective. Its success is due to direct tackling of the aetiological factors.     

Sialadenosis in Patients with Advanced Liver Disease

Sialadenosis (sialosis) has been associated most often with alcoholic liver disease and alcoholic cirrhosis, but a number of nutritional deficiencies, diabetes, and bulimia have also been reported to result in sialadenosis. The aim of this study was to determine the prevalence of sialadenosis in patients with advanced liver disease. Patients in the study group consisted of 300 candidates for liver transplantation. Types of liver disease in subjects with clinical evidence of sialadenosis were compared with diagnoses in cases who had no manifestations of sialadenosis. The data were analyzed for significant association. Sialadenosis was found in 28 of the 300 subjects (9.3%). Among these 28 cases, 11 (39.3%) had alcoholic cirrhosis. The remaining 17 (60.7%) had eight other types of liver disease. There was no significant association between sialadenosis and alcoholic cirrhosis (P = 0.389). These findings suggest that both alcoholic and non-alcoholic cirrhosis may lead to the development of sialadenosis. Advanced liver disease is accompanied by multiple nutritional deficiencies which may be exacerbated by alcohol. Similar metabolic abnormalities may occur in patients with diabetes or bulimia. Malnutrition has been associated with autonomic neuropathy, the pathogenic mechanism that has been proposed for sialadenosis.     

Serum Circ‐FAF1/Circ‐ELP3: A novel potential biomarker for breast cancer diagnosis

BackgroundRecently, measurement of serum circular RNAs (circRNAs) as a non‐invasive tumor marker has been considered more. We designed the present study to investigate the diagnostic efficiency of serum Circ‐ELP3 and Circ‐FAF1, separately and simultaneously, for diagnosis of patients with breast cancer.MethodsSeventy‐eight female patients diagnosed as primary breast cancer participated in this study. We measured the level of circRNAs in serum specimens of the studied subjects. A receiver operating characteristic (ROC) curve was plotted and the diagnostic efficiency for both circRNAs was determined.ResultsCompared to non‐cancerous controls, Circ‐ELP3 was upregulated in breast cancer patients (p‐value = 0.004). On the other hand, serum Circ‐FAF1 was seen to be decreased in breast cancer patients than controls (p‐value = 0.001). According to ROC curve results, the area under the curve (AUC) for Circ‐ELP3 and Circ‐FAF1 was 0.733 and 0.787, respectively. Furthermore, the calculated sensitivity and specificity for Circ‐ELP3 and Circ‐FAF1 were 65, 64% and 77, 74%, respectively. Merging both circRNAs increased the diagnostic efficiency, with a better AUC, sensitivity and specificity values of 0.891, 96 and 62%, respectively.ConclusionBriefly, our results revealed the high diagnostic value for combined circRNAs panel, including Circ‐ELP3 and Circ‐FAF1 as a non‐invasive marker, in detection of breast carcinomas.     

Is there relationship between serum uric acid levels and lower urinary tract symptoms,prostate volume,and PSA in men without cancer? A prospective population-based study

There are conflicting results about uric acid (UA) effect on the prostate. We investigated the relationship between UA and PSA, free PSA, prostate volume and international prostate symptoms score (IPSS) in benign prostate hyperplasia (BPH). This study was conducted in BPH men without cancer who were referred for annual health workup (N = 910) from 2017 to 2020. The mean ages were 67.28 ± 9.2 years. UA was positively related to IPSS and PSA (r = 0.210, p = .023 and r = 0.156, p = .041 respectively) and also negatively related to free/total PSA ratio (r = −0.332, p = .01) but not related to prostate volume (r = 0.036, p = .696). After adjustment for age, BMI and prostate volume, there were significant relationships between hyperuricaemia and PSA, free/total PSA ratio, and IPSS (95% CI: 0.254–1.645, OR = 0.647, p = .039; 95% CI: 0.076–0.899, OR = 0.270, p = .033 and 95% CI: 1.011–3.386, OR = 1.851, p = .038 respectively). These results should be considered during the general assessment of the patients with BPH. The findings raise the possible hypothesis of relationship between serum UA with IPSS and PSA which should be investigated by future studies.