Low osteotomy cut of Dega procedure for older children with developmental dysplasia of the hip.

The effect on acetabular management in developmental dysplasia of the hip (DDH) patients aged 7 or older with modified low Dega osteotomy procedure was evaluated. Patients between 7 and 14 years old were managed with modified low Dega osteotomy and open reduction and concomitant procedures to evaluate whether low level osteotomy improved the clinical and radiologic outcomes after treatment. Clinical status was assessed using the modified McKay's criteria; radiologic evaluations were assessed for the modified Severin classification, the mean acetabular index (AI), Sharp angle and center-edge (CE) angle. And occurrence of triradiate cartilage injury and complications was recorded. Forty-two DDH patients (57 hips) between 7 and 14 years old were managed with modified low Dega osteotomy. The results demonstrated the latest follow-up 43 hips (75.4%) were rated excellent and 10 hips (17.5%) rated good according to the modified McKay criteria and 41 hips (71.9%) were rated excellent and 11 hips (19.3%) rated good according to Modified Severin classification, respectively. The mean Hip Score improved from 69.53 ±â€…7.14 before the operation to 93.17 ±â€…8.43 at the final follow-up. The mean AI changed from 31.9° to 20.2°, mean Sharp angle decreased from 59.3° to 38.8° and mean CE angle increased from -10.9° to 35.2°, preoperatively and at latest follow-up, respectively. The modified low Dega osteotomy combined with open reduction and concomitant procedures were found to be adequate in improving instant and sustained clinical and radiographic outcomes for the late detected pediatric walking DDH patients.

The Periosteal Autografts Transplantation for Cartilage Defects of the Hip in Older Children With Developmental Dysplasia as an Adjunctive Procedure.

Cartilage lesions are at a high prevalence in dysplastic hips and may relate to arthritic changes and hip joint dysfunction. To date, the effectiveness of repair of articular cartilage defects in the dysplastic hips has not yet been thoroughly evaluated. Here we retrospectively reviewed the effects of acetabuloplasty procedures with/without concomitant autologous tibial periosteal transplantation (ATPT) for articular cartilage defects of the hip in older children with developmental dysplasia of the hip (DDH).Older DDH children with focal cartilage defects of the acetabular or femoral cartilage or both in the hip joint were treated by acetabuloplasty procedures with (Group I) or without (Group II) concomitant ATPT to evaluate the improvements in range of motion (ROM), pain relief of hip, walking tolerability (WL), radiologic evaluations, and outcomes in the long-term follow-up.More satisfactory functional outcome is readily achieved among patients treated with combined acetabuloplasty and ATPT, evidenced by marked pain relief and improved ROM and WL. The latest favorable radiologic evaluation was 70.6% in Group I and 60.0% in Group II, respectively. More hips exhibited congruency between the femoral head and the shell, with less deformity of femoral head and acetabulum or narrowed joint space in Group I. Few major complications were recorded in Group I.Application of periosteal autograft for repair of cartilage defects within the hip joint might be an effective adjunctive treatment for acetabuloplasty in preventing stiffness, reducing pain, and improving ROM and outcomes in hip rehabilitation in the long-term follow-up in older children with DDH.

Electroacupuncture activates enteric glial cells and protects the gut barrier in hemorrhaged rats.

AIM: To investigate whether electroacupuncture ST36 activates enteric glial cells, and alleviates gut inflammation and barrier dysfunction following hemorrhagic shock. METHODS: Sprague-Dawley rats were subjected to approximately 45% total blood loss and randomly divided into seven groups: (1) sham: cannulation, but no hemorrhage; (2) subjected to hemorrhagic shock (HS); (3) electroacupuncture (EA) ST36 after hemorrhage; (4) vagotomy (VGX)/EA: VGX before hemorrhage, then EA ST36; (5) VGX: VGX before hemorrhage; (6) α-bungarotoxin (BGT)/EA: intraperitoneal injection of α-BGT before hemorrhage, then EA ST36; and (7) α-BGT group: α-BGT injection before hemorrhage. Morphological changes in enteric glial cells (EGCs) were observed by immunofluorescence, and glial fibrillary acidic protein (GFAP; a protein marker of enteric glial activation) was evaluated using reverse transcriptase polymerase chain reaction and western blot analysis. Intestinal cytokine levels, gut permeability to 4-kDa fluorescein isothiocyanate (FITC)-dextran, and the expression and distribution of tight junction protein zona occludens (ZO)-1 were also determined. RESULTS: EGCs were distorted following hemorrhage and showed morphological abnormalities. EA ST36 attenuated the morphological changes in EGCs at 6 h, as compared with the VGX, α-BGT and HS groups. EA ST36 increased GFAP expression to a greater degree than in the other groups. EA ST36 decreased intestinal permeability to FITC-dextran (760.5 ± 96.43 ng/mL vs 2466.7 ± 131.60 ng/mL, P < 0.05) and preserved ZO-1 protein expression and localization at 6 h after hemorrhage compared with the HS group. However, abdominal VGX and α-BGT treatment weakened or eliminated the effects of EA ST36. EA ST36 reduced tumor necrosis factor-α levels in intestinal homogenates after blood loss, while vagotomy or intraperitoneal injection of α-BGT before EA ST36 abolished its anti-inflammatory effects. CONCLUSION: EA ST36 attenuates hemorrhage-induced intestinal inflammatory insult, and protects the intestinal barrier integrity, partly via activation of EGCs.

Electroacupuncture ST36 prevents postoperative intra-abdominal adhesions formation.

BACKGROUND: We have recently proved electroacupuncture (EA) ST36 exerted an anti-inflammatory effect in the early phase of intra-abdominal adhesion formation. Evidences indicate that the anti-inflammatory effect of EA ST36 involves a cholinergic anti-inflammatory pathway-dependent mechanism via the vagus nerve. However, the exact effects and accurate vagal modulation of acupuncture in prevention of postoperative intra-abdominal adhesion formation has not been thoroughly evaluated. MATERIALS AND METHODS: Sprague-Dawley rats subjected to abdominal adhesion lesions operation at the cecum and abdominal wall were randomly divided into six groups as follows: (a) EAN: EA non-channel acupoints; (b) EA: EA ST36 after abdominal lesions; (c) VGX/EA: vagotomy (VGX) after abdominal lesions, then EA ST36; (d) VGX/EAN: VGX after abdominal lesions, then EAN; (e) α-BGT/EA: intraperitoneal injection of α-bungarotoxin (α-BGT, an antagonist of α7 subunit of cholinergic nicotinic receptor) before EA ST36, and (f) α-BGT/EAN group: α-BGT injection before EAN. Seven days after abdominal surgical lesions, the levels of tumor necrosis factor-α (TNF-α) and vascular endothelial growth factor (VEGF) in the adhesive tissue were evaluated, macroscopic observation and histopathologic evaluation of adhesion formation and assessment of angiogenesis by immunohistochemical staining of platelet endothelial cell adhesion molecule-1 (CD31) were performed. RESULTS: EA ST36 reduced TNF-α and VEGF levels in adhesive tissue homogenates 7 d after surgery, whereas vagotomy or intraperitoneal injection of α-BGT before EA ST36 reversed its suppressive effects. EA at non-channel acupoints with or without vagotomy or intraperitoneal injection of α-BGT before EA had no suppressive effects on TNF-α and VEGF levels. EA ST36 alleviated the adhesion formation, with both of macroscopic and histopathologic adhesion scores significantly lower than those of the EAN group (1.56 ± 0.29 versus 3.00 ± 0.82, 1.35 ± 0.4 versus 3.91 ± 0.8, respectively, both P < 0.05). Compared with the EAN group, EA ST36 significantly decreased angiogenesis evidenced by reduced CD31 positive microvessel density in adhesive tissue. CONCLUSIONS: EA ST36 might reduce the postoperative local inflammatory response, attenuate the angiogenesis, and alleviate the adhesion formation partly via activating the cholinergic anti-inflammatory mechanism.

PNU-282987 improves the hemodynamic parameters by alleviating vasopermeability and tissue edema in dogs subjected to a lethal burns shock.

Excessive inflammation and high vasopermeability can lead to blood volume loss and tissue edema, which can affect the resuscitation and prognosis for serious burn patients. In this experiment, we investigated the effect of PNU-282987, an α7 nicotine cholinergic receptor agonist on the hemodynamic parameters and survival rate by inhibiting vasopermeability and tissue edema during the fluid resuscitation for lethal burn shock. Forty Beagle dogs with intubation of the carotid artery and jugular vein 24 hours before the injury were subjected to 50% TBSA full-thickness burns, and were randomly divided into following four groups: no resuscitation group (group NR), venous fluid resuscitation group (group R), PNU-282987 treatment group (group P), and fluid resuscitation group plus PNU-282987 group (group RP), with 10 dogs in each group. Hemodynamic variables and biochemical parameters were determined with animals in a conscious and cooperative state. The plasma volume and the vasopermeability were determined by indocyanine green and fluorescein isothiocyanate-dextran, respectively. The level of tumor necrosis factor-α and interleukin-1ß in plasma, and the water content of different organs were also determined. The mean arterial pressure, cardiac output, and plasma volume of all dogs decreased significantly, and the lung extravascular water index and pulmonary vascular permeability index increased remarkably after burn. The hemodynamic parameters deteriorated continually in group N dogs, and then anuria, hyperlactacidemia, and multiple organ dysfunctions developed. The mean arterial pressure and cardiac output of dogs in group R and group RP returned to preinjury levels at 48 hours postburn. The lung extravascular water index and pulmonary vascular permeability in group R were higher than those before preinjury. The dogs in group RP were found to have a significant increase in plasma volume and urine output, and a remarkable decrease in the levels of tumor necrosis factor-α, interleukin-1α, lactic acid, and organ functions compared with those of group R (P <.05). The survival rate of RP group (100%; 10/10) was significantly higher than that of group N (0; 0/10), group P (20%; 2/10), and group R (60%; 6/10). PNU-282987 combined with intravenous fluid resuscitation significantly improved hemodynamics and the survival rate in the early period after this lethal burn shock. The mechanism may be attributable to the lowering of the level of proinflammatory mediators, amelioration of vasopermeability-induced visceral edema, less of blood volume loss, and protection of vital organs through activation of cholinergic anti-inflammatory pathway.

Electroacupuncture improves gut barrier dysfunction in prolonged hemorrhagic shock rats through vagus anti-inflammatory mechanism.

AIM: To investigate whether electroacupuncture (EA) at Zusanli (ST36) prevents intestinal barrier and remote organ dysfunction following prolonged hemorrhagic shock through a vagus anti-inflammatory mechanism. METHODS: Sprague-Dawley rats were subjected to about 45% of total blood volume loss followed by delayed fluid replacement (DFR) with Ringer lactate 3h after hemorrhage. In a first study, rats were randomly divided into six groups: (1) EAN: EA at non-channel acupoints followed by DFR; (2) EA: EA at ST36 after hemorrhage followed by DFR; (3) VGX/EA: vagotomy (VGX) before EA at ST36 and DFR; (4) VGX/EAN: VGX before EAN and DFR; (5) α-bungarotoxin (α-BGT)/EA: intraperitoneal injection of α-BGT before hemorrhage, followed by EA at ST36 and DFR; and (6) α-BGT/EAN group: α-BGT injection before hemorrhage followed by EAN and DFR. Survival and mean arterial pressure (MAP) were monitored over the next 12 h. In a second study, with the same grouping and treatment, cytokine levels in plasma and intestine, organ parameters, gut injury score, gut permeability to 4 kDa FITC-dextran, and expression and distribution of tight junction protein ZO-1 were evaluated. RESULTS: MAP was significantly lowered after blood loss; EA at ST36 improved the blood pressure at corresponding time points 3 and 12 h after hemorrhage. EA at ST36 reduced tumor necrosis factor-α and interleukin (IL)-6 levels in both plasma and intestine homogenates after blood loss and DFR, while vagotomy or intraperitoneal injection of α-BGT before EA at ST36 reversed its anti-inflammatory effects, and EA at ST36 did not influence IL-10 levels in plasma and intestine. EA at ST36 alleviated the injury of intestinal villus, the gut injury score being significantly lower than that of EAN group (1.85 ± 0.33 vs 3.78 ± 0.59, P < 0.05). EA at ST36 decreased intestinal permeability to FITC-dextran compared with EAN group (856.95 ng/mL ± 90.65 ng/mL vs 2305.62 ng/mL ± 278.32 ng/mL, P < 0.05). EA at ST36 significantly preserved ZO-1 protein expression and localization at 12 h after hemorrhage. However, EA at non-channel acupoints had no such effect, and abdominal vagotomy and α-BGT treatment could weaken or eliminate the effects of EA at ST36. Besides, EA at ST36 decreased blood aminotransferase, MB isoenzyme of creatine kinase and creatinine vs EAN group at corresponding time points. At the end of 12-h experiment, the survival rate of the EA group was significantly higher than that of the other groups. CONCLUSION: EA at ST36 attenuates the systemic inflammatory response, protects intestinal barrier integrity, improves organ function and survival rate after hemorrhagic shock via activating the cholinergic anti-inflammatory mechanism.

Valproic acid treatment inhibits hypoxia-inducible factor 1α accumulation and protects against burn-induced gut barrier dysfunction in a rodent model.

OBJECTIVE: Burn-induced gut dysfunction plays an important role in the development of sepsis and multiple organ dysfunction. Emerging evidence suggests that hypoxia-inducible factor-1α (HIF-1α) is critical in paracellular barrier functions via regulating vascular endothelial growth factor (VEGF) and myosin light chain kinase (MLCK) expression. Previous studies have also demonstrated that histone deacetylase inhibitors (HDACIs) can repress HIF-1α. This study aims to examine whether valproic acid (VPA), a HDACI, protects against burn-induced gut barrier dysfunction via repressing HIF-1α-dependent upregulation of VEGF and MLCK expression. METHODS: Rats were subjected to third degree 55% TBSA burns and treated with/ without VPA (300 mg/kg). Intestinal barrier dysfunction was evaluated by permeability of intestinal mucosa to fluorescein isothiocyanate (FITC)-dextran and histologic evaluation. Histone acetylation, tight junction protein zonula occludens 1 (ZO-1), VEGF, MLCK and HIF-1α were measured. In addition, CaCO2 cells were transfected with siRNA directed against HIF-1α and were stimulated with CoCl2 (1mM) for 24 hours with/without VPA (2mM) followed by analysis of HIF-1α, MLCK, VEGF and ZO-1. RESULTS: Burn insults resulted in a significant increase in intestinal permeability and mucosal damage, accompanied by a significant reduction in histone acetylation, ZO-1, upregulation of VEGF, MLCK expression, and an increase in HIF-1α accumulation. VPA significantly attenuated the increase in intestinal permeability, mucosa damage, histone deacetylation and changes in ZO-1 expression. VPA also attenuated the increased VEGF, MLCK and HIF-1α protein levels. VPA reduced HIF-1α, MLCK and VEGF production and prevented ZO-1 loss in CoCl2-stimulated Caco-2 cells. Moreover, transfection of siRNA directed against HIF-1α led to inhibition of MLCK and VEGF production, accompanied by upregulation of ZO-1. CONCLUSIONS: These results indicate that VPA can protect against burn-induced gut barrier dysfunction. These protective effects may be due to its inhibitory action on HIF-1α, leading to a reduction in intestinal VEGF and MLCK expression and minimizing ZO-1 degradation.

Electroacupuncture at Zusanli (ST36) Prevents Intestinal Barrier and Remote Organ Dysfunction following Gut Ischemia through Activating the Cholinergic Anti-Inflammatory-Dependent Mechanism.

This study investigated the protective effect and mechanism of electroacupuncture at ST36 points on the intestinal barrier dysfunction and remote organ injury after intestinal ischemia and reperfusion injury in rats. Rats were subjected to gut ischemia for 30 min, and then received electroacupuncture for 30 min with or without abdominal vagotomy or intraperitoneal administration of cholinergic α 7 nicotinic acetylcholine receptor ( α 7nAChR) inhibitor. Then we compared its effects with electroacupuncture at nonchannel points, vagal nerve stimulation, or intraperitoneal administration of cholinergic agonist. Cytokine levels in plasma and tissue of intestine, lung, and liver were assessed 60 min after reperfusion. Intestinal barrier injury was detected by histology, gut injury score, the permeability to 4 kDa FITC-dextran, and changes in tight junction protein ZO-1 using immunofluorescence and Western blot. Electroacupuncture significantly lowered the levels of tumor necrosis factor- α and interleukin-8 in plasma and organ tissues, decreased intestinal permeability to FITC-dextran, and prevented changes in ZO-1 protein expression and localization. However, abdominal vagotomy or intraperitoneal administration of cholinergic α 7nAChR inhibitor reversed these effects of electroacupuncture. These findings suggest that electroacupuncture attenuates the systemic inflammatory response through protection of intestinal barrier integrity after intestinal ischemia injury in the presence of an intact vagus nerve.

[Effects of acupuncture at "Zusanli" (ST 36) on cerebral proinflammatory cytokine and plasma neuron specific enolase in septic rats].

OBJECTIVE: To explore protective effects of acupuncture at "Zusanli" (ST 36) on cerebral tissue in rats with sepsis. METHODS: Cecal ligation and puncture (CLP) was applied to duplicate the rat model of sepsis. According to random number table, thirty SD rats were divided into a sepsis model group (group A), a sepsis model plus electroacupuncture (EA) group (group B), and a sepsis model plus non-acupoint EA group (group C), ten rats in each one. EA with the same frequency and intensity at "Zusanli" (ST 36) and non-acupoint (0.5 cm laterally to "Zusanli") for 30 min was applied in the group B and group C, respectively. No treatment was given in the goup A. 6 hours after CLP, blood was acquired from abdominal aorta to measure the levels of neuron specific enolase (NSE). Then the rats were sacrificed by abdominal aorta exsanguination to take their cerebral tissue for measuring the levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6). RESULTS: Six hours after CLP, the level of NSE was (3.51 +/- 0.39) ng/mL in group B, which was significantly lower than (7.72 +/- 0.64) ng/mL in group A (P<0.05). The level of NSE was (8.02 +/- 0.72) ng/mL in the group C, which had no statistical significance with group A (P>0.05). The levels of TNF-alpha, IL-6 in cerebral tissue in group B were significantly lower than that of group A and C (all P>0.05). CONCLUSION: EA at "Zusanli" (ST 36) has certain protective effect on septic rat's brain, which has some relationship with decreasing levels of cerebral tissue proinflammatory cytokine and plasma NSE. EA at non-acupoint has no the same action.

[Effects of PNU282987 on organ function and survival in dogs with lethal burn shock].

OBJECTIVE: To investigate the effects of PNU282987, a α7 nicotinic acetylcholine receptor agonist (α7nAChR), on organ function and survival rate in dogs with lethal burn shock. METHODS: Twelve adult male Beagle dogs were subjected to 50% total body surface area (TBSA) full-thickness flame injury, and then they were randomly divided into a burn group and a PNU282987 group (PNU group), each n=6. The dogs in PNU group received PNU282987 (0.38 mg/kg, venous pumping) and the dogs in burn group received equal amount of normal saline solution as the control group. The mean arterial pressure (MAP) and the plasma levels of tumor necrosis factor-α (TNF-α), alanine aminotransferase (ALT), MB isoenzyme of creatine kinase (CK-MB), creatinine (Cr), blood urea nitrogen (BUN) were continuously determined before and 0.5, 2, 4, 8, 12, 24 hours after burn. All the above measurements were performed with animals in conscious and cooperative state. At the end of 24-hours-period experiment, the survival rate was recorded. RESULTS: The MAP significantly decreased after burn compared with the baseline data before-injury. The level of MAP in PNU group were significantly higher than those of the burn group from 4 hours after burn, and it returned to 83.6% of baseline level at 24 hours. In contrast, those in the burn group progressively decreased with time till death. The plasma levels of TNF-α in PNU group were significantly lower than those of burn group at each time points post injury. The ALT, Cr, BUN and CK-MB of the burn group increased persistently, while those of the PNU group increased at first and decreased subsequently except for ALT increased persistently, and they were all significantly lower than those of the burn group till to the time point of 12 hours (ALT:51.2±7.0 U/L vs. 104.8±7.4 U/L, Cr:42.7±5.4 µmol/L vs. 88.5±4.8 µmol/L, BUN:4.9±1.2 mmol/L vs. 14.7±1.4 mmol/L, CK-MB:564.0±39.1 U/L vs. 734.0±35.9 U/L, all P<0.05). At the end of 24-hours-period experiment, the survival rate of the PNU group was 50% (3/6) and significantly higher than that of the burn group 0(0/6). CONCLUSIONS: The results indicated that PNU282987 decrease the levels of inflammatory cytokine, improve the organ functions and increase 24-hour survival rate in dogs with lethal burn injury. And PNU282987 may have potential clinical application.

Diffuse pulmonary lymphangiomatosis: a case report with literature review.

Diffuse pulmonary lymphangiomatosis (DPL) is a rare disease that is characterized by diffuse proliferation of abnormal pulmonary lymphatic channels. DPL occurs mostly in children and young adults and often undergoes a progressive clinical course, eventually causing deterioration of the lung. Both the clinical diagnosis and treatment of DPL remain a challenge. Here, we report a case of DPL in a 53-year-old Chinese woman with comprehensive investigations including pulmonary function tests, computer tomography (CT), bronchoscopy and histological examination of the lung biopsy, and review the literature.

[Impact of abnormal myoelectricity at gastroduodenal anastomosis on gastric emptying in rats].

OBJECTIVE: To explore the impact of abnormal myoelectricity at gastroduodenal anastomosis on gastric emptying in rats. METHODS: Rats were randomly divided into experimental group (n=16) and control group (n=16). Pylorectomy and end-to-end gastroduodenal anastomosis were performed in the experimental group and electrodes were implanted in the serosal surface adjacent to the anastomosis. Slow waves were recorded by the implanted electrode in vivo. Gastric emptying was examined by scintigraphy. RESULTS: At the first week after surgery, antral slow-wave frequency was significantly lower in the experimental group (0.8±1.4 vs. 3.3±1.2, P<0.01), as was the duodenal slow-wave frequency (2.1±0.6 vs. 11.1±0.7, P<0.01). There was no consecutive slow-waves transduction across the pylorus or the anastomosis. Within 12-16 weeks after operation, antral slow-wave frequency in the experimental group and the control group were (8.7±0.6) cpm and (4.0±0.4) cpm, respectively (P<0.01), and duodenal slow-wave frequency were (11.1±0.8) cpm and (10.8±0.7) cpm, respectively (P>0.05). Retrograde and antegrade myoelectricity transduction through the anastomosis were detected. The mean semi-emptying time in the proximal stomach was 14.7 min in the experimental group and 13.6 min in the control group (P>0.05). Radionuclide retention rate was 25.4% in the experimental group and 39.4% in the control group (P>0.05). The mean semi-emptying time in the distal stomach was 25.3 min in the experimental group and 10.5 min in the control group (P<0.01). Radionuclide retention rate was 46.4% in the experimental group and 18.7% in the control group (P<0.01). CONCLUSION: The abnormal myoelectricity in the region of gastroduodenal stoma may delay liquid gastric emptying in pylorectomy rats.

A novel hGHRH analog and its comparative activity.

Growth hormone releasing hormone is one of the hormones secreted from the hypothalamus. Because of its potential applications in agriculture and medicine, its short half-life and its expensive chemical synthesis, an analog with high GHRH activity and prolonged half-life was sought after. The fusion partner gene with 127 amino acid residues of the C-terminus from L-asparaginase was recombined with asp-pro-hGHRH(1-44) gene synthesized by PCR method to form one kind of fusion protein with unique acid labile linker Asp-Pro. The Pro-hGHRH(1-44) peptide was purified to homogeneity by means of cell disruption, washing, ethanol precipitation, acid hydrolysis, SP-Sephadex C-25, and Sephadex G-10 column chromatography. The peptide's molecular weight of 5,139 Da as measured by EIS-MS was coincident with the actual values. In the study of the activity, the doses of peptide were 0.1, 1.0, and 10 microg/ml for rat pituitary and 5 microg/ml for human pituitary. The peptide increased GH releases from rat pituitary in a concentration-dependent manner (P<0.05; P<0.01). At 1.0 microg/ml, there was a significant difference between Pro-Pro-hGHRH(1-44)-Gly-Gly-Cys and Pro-hGHRH(1-44) or Pro-Pro-hGHRH(1-44) (P<0.05), whereas the standard hGHRH(1-40) showed no measured rGH release. For human fetal pituitary, the Pro-hGHRH(1-44) peptides showed good GH-releasing activity, but there were no significant differences between them. The structure-activity relationship showed that for both rat and human fetal pituitary, the net GH-releasing activity of the Pro-hGHRH(1-44) analog was more than that of Pro-Pro-hGHRH(1-44). The results of the other hormones from human pituitary showed that the analog had good function-selectivity and species specificity.