The molecular mechanism of GADD153 in apoptosis of keloid fibroblasts exposed to botulinum toxin type A.

Apoptosis plays a key role in keloids. Growth arrest and DNA damage-inducible gene 153 (GADD153) is regulated by apoptosis. Botulinum toxin type A (BTXA) can induce apoptosis in keloid fibroblasts. This research aimed to explore the hypothesis that GADD153 mediates apoptosis in keloid fibroblasts exposed to BTXA. BTXA significantly induced GADD153 protein and mRNA expression in keloid fibroblasts. Treatment with c-Jun N-terminal kinase (JNK) inhibitor SP600125, JNK small interfering RNA (siRNA) and tumour necrosis factor-alpha (TNF-α) antibodies reversed the BTXA-induced GADD153 expression. BTXA enhanced the transcriptional activity of GADD153, whereas the GADD153 mutant plasmid, JNK siRNA and anti-TNF-α antibody treatment abolished the BTXA-induced transcriptional activity of GADD153. The addition of TNF-α to keloid fibroblasts markedly increased GADD153 protein expression. The addition of GADD153 siRNA, SP600125 and anti-TNF-α antibodies reversed cell death and caspase 3 and 9 activity induced by BTXA.

Comprehensive Clinical Profile of Mal De Debarquement Syndrome.

BACKGROUND: There has been increasing awareness that post-motion triggered rocking self-vertigo can last for months or years, a disorder known as Mal de Debarquement Syndrome (MdDS). A similar feeling of oscillating self-motion can occur without a motion trigger in some individuals, leading to controversy about whether motion triggered (MT) and non-motion triggered (non-MT) symptoms ultimately represent the same disorder. Recognizing the similarities and differences between MT and non-MT MdDS can prevent unnecessary diagnostic testing and lead to earlier and more effective treatments. METHODS: Standardized questionnaire assessment and follow-up interviews of individuals with persistent MT or non-MT MdDS (>1 month) examined at a University Dizziness Clinic. FINDINGS: Questionnaires were available on 80 individuals with persistent MT MdDS and 42 with non-MT MdDS. Sex distribution (81% female) and age of onset (mean 43.4 ± 12.2 years MT; 42.1 ± 15.2 years non-MT) were comparable between MT and non-MT MdDS (p > 0.05). Mean duration of illness was significantly longer in the non-MT group (82.8 ± 64.2 months) than the MT group (35.4 ± 46.4 months) (p < 0.001). There was no correlation between trigger type and age of onset or duration of illness for MT MdDS. Improvement with re-exposure to motion (driving) was typical for both (MT = 89%, non-MT = 64%), but non-MT individuals more frequently had symptoms exacerbated with motion (MT = 0%; non-MT = 10%). Peri-menstrual and menstrual worsening of symptoms was typical in both MT and non-MT MdDS (each 71%). Both MT and non-MT MdDS exhibited a higher population baseline prevalence of migraine (23% and 38%, respectively). Benzodiazepines and SSRI/SNRIs were helpful in both subtypes of MdDS (>50% individuals with a positive response). Physical therapy was modestly helpful in the MT (56%) subtype but not in non-MT (15%). Vestibular therapy made as many individuals worse as better in MT and none improved in the non-MT group. CONCLUSION: General demographic characteristics and exacerbating factors are similar in MT and non-MT MdDS, but there are differences in the duration of illness, effect of motion on symptoms, and response to therapy. Recognizing clinical features of MdDS subtypes may allow for better tailoring of therapy and potentially serve as classification criteria for new clinical designations.

[Restoration of partial penile defect by scrotal skin flap in combination with penile lengthening].

OBJECTIVE: To evaluate the feasibility and clinical efficacy of a scrotal skin flap in combination with penile lengthening for repairing penile defects. METHODS: From 1999 to 2008, 7 cases (19 to 42 years old) of penile defects were treated by scrotal skin flap in combination with penile lengthening. The average preoperative length of stubbed penis was 2.1 cm in flaccid (range: 1.0 to 3.0 cm) and 4.8 cm in erection (range: 3.0 to 5.5 cm). All cases were treated with penile elongation. And a bilateral scrotal skin flap supplied by anterior scrotal artery (n = 3) or whole anterior scrotum flap (n = 4) was used to cover the exposed penile shaft. The scrotal incision was sutured directly. RESULTS: There was no need for urethra reconstruction. It was simple to obtain the scrotal skin flap. And the operation might be quickly performed with a lesser hemorrhage as compared with penile reconstruction. The scrotal flaps survived without any necrosis and all wounds healed primarily with an excellent contour and erectile function. When followed up for 1 - 5 years, the average preoperative penile length was 6.4 cm in flaccid (range: 5.0 to 7.5 cm) and 9.5 cm in erection (range: 8.0 to 10.5 cm). All cases had normal functions of urination, erection and gonobolia. Five cases had satisfied sexual life and one experienced a sexual life. CONCLUSIONS: The method of restoring partial penile defect with scrotal skin flaps is both simple and efficacious. Reasonable appearance and penile length are restored in most cases with better sensory and erectile functions.

[Anatomic research and clinical application of modified penile elongation: a report of 205 cases].

OBJECTIVE: To investigate the application of penile cavernous bodies elongation combined with fat flap for the treatment of micro-penis. METHODS: Anatomic study was performed to study the thickness of penile suspension ligaments and the relationship between the penile erection stability and the mobilization of cavernous bodies crus. The suspension ligaments were divided and cavernous bodies crus were partially mobilized, so as to release part of the cavernous bodies from inferior ramus of pubis. Then the penis was elongated sufficiently. Local fat flap was transposed to fill the front space of pubis to make sure the effective elongation of penis. RESULTS: 205 cases of micro-penis were treated. The average length of the penis was 4.26 cm in the static state, 8.13 cm in erectile state before operation. After operation, it increased to 8.63 cm in the static state, 12.11 cm in erectile state. CONCLUSIONS: The cavernous bodies can be elongated 1-2 cm more with the modified method, while the stability of penile erection is not affected.

[Expression of neuronal nitric oxide synthase in corpus cavernosum with diabetic erectile dysfunction: experiment with rabbits].

OBJECTIVE: To investigate the expression characteristics of neuronal nitric oxide synthase (nNOS) in the corpus cavernosum of diabetic erectile dysfunction (ED). METHODS: Fifty rabbits underwent single intravenous injection of alloxan (100 mg/kg). Blood glucose, system arterial pressure (SAP), and intracavemosal pressure (ICP) were measured 15, 30, and 45 days later. The rabbits with the blood glucose >10 mmol/L were used as diabetic models and those with the ICP lower than the normal control group by more than 25% were used as diabetic ED models. RT-PCR, immunohistochemistry, and Western-blotting were used to detect the expression of nNOS in the corpus cavemosum. RESULTS: Seven days after the alloxan injection the blood glucose levels of 35 rabbits (70%) were > 10 mmol/L. 40% rabbits (14/35) were were used as diabetic ED models. Compared with control group, the ICP 15, 30, and 45 days after alloxan injection were considerately decreased in diabetic ED rabbits (all P < 0.01), and there was no significant difference in SAP between the two groups (all P > 0.05). The relative values of nNOS mRNA expression 15, 30, and 45 days after alloxan injection of diabetic ED rabbits were 0.670 +/- 0.030, 0.451 +/- 0.012, and 0.206 +/- 0.023 respectively,all significantly lower than those of the control group (0.817 +/- 0.010, 0.814 +/- 0.020, and 0.802 +/- 0.007 respectively, all P < 0.05). Western blotting showed that the relative values of nNOS 15, 30, and 45 days after alloxan injection of the ED rabbits were 0.713 +/- 0.014, 0.424 +/- 0.007, and 0.337 +/- 0.009 respectively, all significantly lower than those of the control group (0.797 +/- 0.015, 0.706 +/- 0.020, and 0. 750 +/- 0.022 respectively, all P < 0.05). CONCLUSION: Decreased expression of nNOS in corpus cavernosum is one of possible pathway of diabetic ED.

[In-vitro differentiation of human testicular round spermatids to elongating spermatids].

OBJECTIVE: To investigate the differentiation of human testicular spermatogenic cells during in vitro culture. METHODS: Testicular cells of obstructive azoospermic patients' testis biopsies were dispersed employing mechanic methods. Then, (1) mixed testicular cells were applied to in vitro culture, and changes of the ratio of elongating spermatids and all round cells were analyzed during mixed cell culture; (2) round spermatids were picked up from the mixed cells employing micromanipulator, followed by differentiation of the isolated round spermatids during microdrop culture. RESULTS: The ratio of the elongating spermatids increased significantly (P < 0.05) after 24 hours of mixed cell culture in HTF medium supplemented with FSH and testosterone. During single round spermatid culture, transformation of the round spermatid to elongating spermatid with newly formed flagellum was observed, and the transformation ratio within 48 hours of microdrop culture was 3.54%. The differentiation of human testicular spermatogenic cells cultured in Vero cell conditioned medium was similar to that cultured in HTF medium. CONCLUSION: Human testicular round spermatids can differentiate to elongating spermatids during in vitro culture. Vero cell conditioned medium does not promote the differentiation of human testicular round spermatids to elongating spermatids.

[Applied anatomic investigation of phalloplasty ].

OBJECTIVE: To investigate the anatomy of penis and its adjacent organ for phalloplasty. METHODS: Anatomic dissection of penis and perineum was performed on 30 adult male cadavers (60 sides). Observation and measurement were focused on the penile length of different parts, the morphological relationship of infundibular ligament and suspensory ligament with penile radix, and the feature of crus penis with relation to the deep penile artery. RESULTS: The average length of the penile shaft was 8.13 cm, the penile radix was 7.67 cm and the crus penis was 5.96 - 5.98 cm. The deep penile artery penetrated into the crus penis at its middle 1/3. The infundibular ligament attached to superficial fascia of the penis and extended downward to the scrotal septum to constitute the suspensory structure for both of them. The suspensory ligament attached to the dorsal deep fascia of the penis. Becoming thicker, the rear part of the suspensory ligament connected firmly to the pubic arcuate ligament to constitute a part of suspensory mechanism for the urethra. There was a part of cavernous body, which was free from either ligament or bony attachment, between the penile radix and the crus penis, where the dorsal artery and nerve of penis turned around from the ventral to the dorsal aspect of the penis and the penile dorsal vain penetrated the urogenital septum, draining into intrapelvic venous plexus. CONCLUSIONS: The divisional measurement of the penis length, the recognition of the suspensory ligaments and the anatomic feature of the crus penis with relation to the deep penile artery are all of significant importance to improve the operation of phalloplasty.

[Penile augmentation using acellular dermal matrix].

OBJECTIVE: Penile enhancement was performed using acellular dermal matrix. METHODS: Multiple layers of acellular dermal matrix were placed underneath the penile skin to enlarge its girth. Since March 2002, penile augmentation has been performed on 12 cases using acellular dermal matrix. RESULTS: Postoperatively all the patients had a 1.3-3.1 cm (2.6 cm in average) increase in penile girth in a flaccid state. The penis had normal appearance and feeling without contour deformities. All patients gained sexual ability 3 months after the operation. One had a delayed wound healing due to tight dressing, which was repaired with a scrotal skin flap. CONCLUSIONS: Penile enlargement by implantation of multiple layers of acellular dermal matrix was a safe and effective operation. This method can be performed in an outpatient ambulatory setting. The advantages of the acellular dermal matrix over the autogenous dermal fat grafts are elimination of donor site injury and scar and significant shortening of operation time.

[Effect of solution viscosity on polymer precorneal residence time evaluated by in vitro method].

AIM: To evaluate how solution viscosity affects the precorneal residence of five water-soluble polymers with different properties. METHODS: Captive bubble technique was used, with the consecutive change of contact angle interpreted as an indication of desorption process, to study the residence of those polymers in vitro on freshly enucleated rabbit eyes under physiological conditions. RESULTS: Carbopol and sodium hyaluronate (HA), which adsorbed to isolated ocular surface more than 15 min, showed the optimum precorneal retentive capabilities. When the solution viscosity increased from 12 mPa.s to 50 mPa.s, the residence time of carbopol and HA were prolonged 10 min and 7 min, respectively, but that of sodium carboxymethylcellulose was not affected. CONCLUSION: The result suggested that higher viscosity is beneficial to improve the ocular residence time of bio-adhesive polymers.