[Analysis of the causes of long-standing pelvic anterior sacral space infection and discussion of management techniques].

Objective: To investigate the causes and management of long-term persistent pelvic presacral space infection. Methods: Clinical data of 10 patients with persistent presacral infection admitted to the Cancer Hospital of Zhengzhou University from October 2015 to October 2020 were collected. Different surgical approaches were used to treat the presacral infection according to the patients' initial surgical procedures. Results: Among the 10 patients, there were 2 cases of presacral recurrent infection due to rectal leak after radiotherapy for cervical cancer, 3 cases of presacral recurrent infection due to rectal leak after radiotherapy for rectal cancer Dixons, and 5 cases of presacral recurrent infection of sinus tract after adjuvant radiotherapy for rectal cancer Miles. Of the 5 patients with leaky bowel, 4 had complete resection of the ruptured nonfunctional bowel and complete debridement of the presacral infection using an anterior transverse sacral incision with a large tipped omentum filling the presacral space; 1 had continuous drainage of the anal canal and complete debridement of the presacral infection using an anterior transverse sacral incision. 5 post-Miles patients all had debridement of the presacral infection using an anterior transverse sacral incision combined with an abdominal incision. The nine patients with healed presacral infection recovered from surgery in 26 to 210 days, with a median time of 55 days. Conclusions: Anterior sacral infections in patients with leaky gut are caused by residual bowel secretion of intestinal fluid into the anterior sacral space, and in post-Miles patients by residual anterior sacral foreign bodies. An anterior sacral caudal transverse arc incision combined with an abdominal incision is an effective surgical approach for complete debridement of anterior sacral recalcitrant infections.

[Reoperation and perioperative management of residual cyst wall with perineal intractable sinus after resection of presacral cyst tumors].

Objective: To investigate the reoperation and perioperative management of residual cyst wall with perineal intractable sinus after resection of presacral cyst tumors. Methods: The clinical data of 29 patients with residual cyst wall and perineal intractable sinus after resection of presacral cyst tumors in Affiliated Cancer Hospital of Zhengzhou University from January 2014 to August 2019 were reviewed, including the characteristics of the residual cyst wall with perineal intractable sinus after resection of presacral cyst tumors, surgical method, and perioperative management. Results: Twenty-nine patients with residual cyst wall and perineal intractable sinus after resection of presacral cyst tumors, including 9 cases of epidermoid cysts, 7 cases of dermoid cysts, 10 cases of mature teratomas and 3 cases of malignant cysts (including malignant transformation of caudate cyst and teratoma); The 29 patients underwent posterior approaches for cyst resection in other hospital before, of whom 1 patient underwent posterior combined with transabdominal approach. All of thes patients underwent resection of residual presacral cyst wall and perineal intractable sinus in our hospital, of whom 25 patients underwent a transperineal approach through an arc-shaped incision anterior to the apex of the coccyx, and the other 4 patients underwent transperineal arc-shaped incision combined with transabdominal approach. All of the patients were cured without serious complications occurring, postoperative pathological and the magnetic resonance imaging diagnosis showed that the residual cyst wall and perineal intractable sinus were all completely removed. Conclusion: Appropriate surgical approache and perioperative treatment for the patients with residual cyst wall and perineal intractable sinus are very important to promote the resection of residual cyst wall and the healing of perineal intractable sinus.

[Association between serum lipid level and depression in patients with chronic heart failure].

Objective: To investigate the association between serum lipid level and depression in patients with chronic heart failure (CHF). Methods: A total of 348 patients with CHF from the First department of Cardiology of the people's hospital of Shaanxi province from September 2016 to June 2017 were included.The Hamilton Depression Scale (HAMD) was used to evaluate the degree of depression and some related clinical data were tested.The serum lipid level and depression scores in the patients were analyzed using Pearson correlation analysis, and Logistic regression analysis was used to analyze the confounding factors of depression. Results: There was significant difference in the proportion of depression between normal serum lipid group and dyslipidemia group (P=0.044). Pearson correlation analysis showed that depression score was linearly related to total cholesterol (r=0.326, P<0.001) and low density lipoprotein cholesterol (r=0.354, P<0.001), and Logistic regression analysis showed that after adjusting for age, BMI, triglyceride, low density lipoprotein cholesterol, creatinine, total bilirubin, albumin, B type natriuretic peptide, total cholesterol (OR=3.523, P=0.007) and high density lipoprotein cholesterol (OR=0.205, P=0.041) were associated with depression in CHF patients. Conclusion: Total cholesterol can increase the risk of depression, and high density lipoprotein cholesterol can reduce the risk of depression in CHF patients.

The microRNA expression profile in porcine skeletal muscle is changed by constant heat stress.

Heat stress has profound effects on animal performance and muscle function, and microRNAs (miRNAs) play a critical role in muscle development and stress responses. To characterize the changes in miRNAs in skeletal muscle responding to heat stress, the miRNA expression profiles of longissimus dorsi muscles of pigs raised under constant heat stress (30 °C; n = 8) or control temperature (22 °C; n = 8) for 21 days were analyzed by Illumina deep sequencing. A total of 58 differentially expressed miRNAs were identified with 30 down-regulated and 28 up-regulated, and 63 differentially expressed target genes were predicted by miRNA-mRNA joint analysis. GO and KEGG analyses showed that the genes regulated by differentially expressed miRNAs were enriched in glucose metabolism, cytoskeletal structure and function and stress response. Real-time PCR showed that the mRNA levels of PDK4, HSP90 and DES were significantly increased, whereas those of SCD and LDHA significantly decreased by heat exposure. The protein levels of CALM1, DES and HIF1α were also significantly increased by constant heat. These results demonstrated that the change in miRNA expression in porcine longissimus dorsi muscle underlies the changes in muscle structure and metabolism in porcine skeletal muscle affected by constant heat stress.

Effects of heat shock protein 90 expression on pectoralis major oxidation in broilers exposed to acute heat stress.

This study was conducted to determine the effects of heat shock protein 90 (HSP90) expression on pH, lipid peroxidation, heat shock protein 70 (HSP70), and glucocorticoid receptor (GR) expression of pectoralis major in broilers exposed to acute heat stress. In total, 90 male broilers were randomly allocated to 3 groups: control (CON), heat stress (HS), or geldanamycin treatment (GA). On d 41, the broilers in the GA group were injected intraperitoneally with GA (5 µg/kg of BW), and the broilers in the CON and HS groups were injected intraperitoneally with saline. Twenty-four hours later, the broilers in the CON group were moved to environmental chambers controlled at 22°C for 2 h, and the broilers in the HS and GA groups were moved to environmental chambers controlled at 40°C for 2 h. The pH values of the pectoralis major after 30 min and 24 h of chilling after slaughter of HS and GA broilers were significantly lower (P < 0.01) than those of the CON broilers. Heat stress caused significant increases in sera corticosterone and lactic dehydrogenase, the activity of malondialdehyde and superoxide dismutase, the expression of HSP90 and HSP70, and nuclear expression of GR protein in the pectoralis major (P < 0.05). Heat stress induced a significant decrease in GR protein expression in the cytoplasm and GR mRNA expression. Furthermore, the low expression of HSP90 significantly increased levels of lactic dehydrogenase and malondialdehyde and GR protein expression in the cytoplasm under heat stress (P < 0.01), and significantly decreased nuclear GR protein expression (P < 0.01). Heat shock protein 90 was positively correlated with corticosterone and superoxide dismutase activities (P < 0.01), and HSP90 mRNA was negatively correlated with pH after chilling for 24 h. The results demonstrated that HSP90 plays a pivotal role in protecting cells from oxidation.

[A multicenter prospective clinical trial on the effect of domestic bone level implants on single tooth implantation and restoration].

Objective: To evaluate the clinical application effects of a domestic bone-level implant system for restoring single tooth loss, and provide clinical evidence for the promotion and application of domestic implants. Methods: A prospective, multicenter clinical trial was conducted from April 2018 to January 2020 in three institutions: Department of Oral Implantology, School & Hospital of Stomatology, Wuhan University, Department of Stomatology, The First Affiliated Hospital of Zhejiang University School of Medicine, and Department of Stomatology, The Third Hospital of Hebei Medical University. The trial planned to include 100 patients for single tooth implantation and restoration, followed up for 1 year, to evaluate the implantation success rate and other related outcomes. Results: This study screened a total of 142 patients and ultimately included 100, comprising 43 males and 57 females with age of (47.0±12.2) years. Ninety-eight out of 100 patients completed a one-year follow-up (98.0%), while 2 patients terminated the trial early due to implant loosening (2.0%). After a one-year follow-up, the implants of the 98 patients were all functioning successfully, with a success rate of 98.0% (98/100). The patients were satisfied with the overall restoration effect. Conclusions: This study indicates that the domestic bone-level implant system has achieved favorable short-term clinical outcomes for single-tooth implantation and restoration.

Screening of differentially expressed genes of middle cerebral artery occlusion with DNA microarray.

OBJECTIVES: To screen differentially expressed genes of different days after cerebral artery occlusion and drug treatment, and identify related small drug molecules. MATERIALS AND METHODS: The gene expression profile GSE35338 of cerebral artery occlusion was downloaded from Gene Expression Omnibus database, including a total of 14 samples. 5 samples are 1 day after cerebral artery occlusion (control), 3 samples are 7 days after cerebral artery occlusion and 3 samples are under lipopolysaccharide (LPS) treatment. Differentially expressed genes (DEGs) between different days after cerebral artery occlusion were screened (p < 0.05, FDR < 0.05, |logFC| > 1). The DEGs were then entered into the CMAP database and related small drug molecules were retrieved, followed by calculation of co-expression score of the genes and construction of co-expression-drug network. FuncAssociate software and DAVID were used to obtain the functional clusters of genes with p-value < 0.05 and FDR < 0.05. RESULTS: Compared with the control group, 825, 1445, 218 DEGs and 4, 3, 2 most-related small drug molecules were respectively identified from 3, 7 days after cerebral artery occlusion and LPS treated group. Co-expression network was constructed and functional clusters were found to be 161, 146, and 6 in each group. CONCLUSIONS: Our study provides some underlying biomarkers for cerebral artery occlusion under varied conditions and potential small drug molecules for treatment of cerebral artery occlusion.

Overexpression of heat shock protein 70 and its relationship to intestine under acute heat stress in broilers: 2. Intestinal oxidative stress.

Oxidative stress injury is one important factor in intestinal mucosal barrier damage. Expression of heat shock protein (HSP)70 is an endogenous mechanism by which living cells adapt to stress. This study was undertaken to investigate the protective effects of HSP70 on intestinal oxidative stress. Two hundred and forty broilers were injected intraperitoneally with HSP70 inducer l-(1)-glutamine or with the inhibitor quercetin. Twenty-four hours later, they were heat stressed for 0, 2, 3, 5, and 10 h, respectively, at 36 ± 1°C. The l-(1)-glutamine significantly increased HSP70 expression (P < 0.001). At 2 h or 3 h of heat stress, the HSP70 expression obviously elevated (P < 0.001). Levels of corticosterone and the heterophil:lymphocyte ratio significantly increased when HSP70 expression was inhibited (P < 0.0001). Serum corticosterone was negatively correlated with the HSP70 expression at 3 h of heat stress (P = 0.0015; R = -0.6537). Heat shock protein 70 significantly protected the integrity of the intestinal mucosa from heat stress, with significantly decreased lactic dehydrogenase when HSP70 expression was enhanced (P < 0.001). In addition, heat-stress time significantly affected the lactic dehydrogenase release (P < 0.001). Furthermore, HSP70 significantly elevated antioxidant enzyme activities (such as superoxide dismutase, glutathione peroxidase, and total antioxidant capacity) and inhibited lipid peroxidation to relieve intestinal mucosal oxidative injury (P < 0.001). These results suggest that HSP70 is capable of protecting the intestinal mucosa from heat-stress injury by improving antioxidant capacity of broilers and inhibiting the lipid peroxidation production.

Overexpression of heat shock protein 70 and its relationship to intestine under acute heat stress in broilers: 1. Intestinal structure and digestive function.

The objective of this study was to investigate the relationship between heat shock protein 70 (HSP70) overexpression and intestinal structure and digestive function in heat-stressed broilers. In total, 240 male broilers were injected intraperitoneally with l-(1)-glutamine (0.75 mg/kg of BW) or quercetin (5 mg/kg of BW). Twenty-four hours later, they were heat-stressed for 0, 2, 3, 5, and 10 h, respectively, under 36 ± 1°C. The HSP70 protein and mRNA expression were obviously elevated at 3 h of heat stress, and glutamine induced the overexpression of HSP70 in the jejunal mucosa at different heat-stress times (P < 0.01). No significant change of jejunal villus height, crypt, and villus height:crypt ratio were observed after heat stress, and there were no effects of HSP70 overexpression on intestinal morphology under heat stress. The overexpression of HSP70 significantly increased alkaline phosphatase activity at 3 h of heat stress (P < 0.01). There was a strong correlation between HSP70 expression and the digestive enzyme activity (P ≤ 0.001). The overexpression of HSP70 significantly increased the amylase, lipase, and trypsin activity under heat stress (P < 0.001). These results demonstrated that glutamine was a good HSP70 enhancer to establish an HSP70 overexpression model. Although the overexpression of HSP70 did not change intestinal morphology conditions, it significantly increased broiler digestive enzyme activity under heat stress.

[Progress in biomodification of dentin type â collagen by different types of cross-linkers].

Establishing a stable resin-dentin hybrid layer is an effective method to improve the adhesion durability of the restoration. The biomodification of dentin by cross-linkers can enhance the mechanical properties of collagen and resistance to enzymatic hydrolysis while, inhibiting the process of demineralization and promoting the remineralization of dentin, which has the potential clinical applicability of preventing dental caries and improving adhesive property. This review summarizes the biomodification of dentin type Ⅰ collagen by different cross-linkers.

[Effect of adenosine triphosphate on type â collagen mineralization in hard tissue].

Objective: To observe the effect of adenosine triphosphate (ATP) phosphorylation on type Ⅰ collagen mineralization and explore the role of small molecule compound ATP in biomimetic mineralization. Methods: Fourier transform infrared spectroscopy (FT-IR) was used to analyze the phosphorylation of collagen molecules by different concentrations (0, 25, 50, 100 mmol/L) of ATP. The concentration of 50 mmol/L ATP was chosen to construct the phosphorylated collagen mineralization model. Transmission electron microscopy (TEM) was used to observed the ultrastructure of mineralized collagen and the collagen mineralization rate was further calculated by ImageJ software. The surface morphology of the collagen gel ATP group and the control group was observed by scanning electron microscopy (SEM) and the elemental analysis was performed by using an X-ray energy spectrometer. The artificial demineralized dentin samples were mineralized for 2 days and 4 days to compare the effect of ATP on dentin remineralization by SEM. Results: FT-IR analysis showed that the formation of new peaks at wavenumbers of 642, 818, and 902 cm(-1) indicated that ATP can phosphorylate type Ⅰ collagen. Through TEM and SEM observation, the mineralization degree of type Ⅰ collagen and demineralized dentin pretreated with 50 mmol/L ATP were significantly higher than that of the control group. Compared with the control group [(31.65±1.62)%], the mineralization rate of collagen in the ATP group [(100±0)%] was significantly increased after 2 days of mineralization (P<0.05). Conclusions: ATP phosphorylation can effectively promote the mineralization process of type Ⅰ collagen.

The proteasome inhibitor bortezomib inhibits intimal hyperplasia of autologous vein grafting in rat model.

OBJECTIVE: Increasing evidence indicates that inflammation plays an important role in intimal hyperplasia (IH) induced by autologous vein grafts. The proteasome inhibitor bortezomib shows anti-inflammatory effects, so we used an autologous vein transplantation model to test whether bortezomib inhibits neointimal formation in transplant-induced vasculopathy. MATERIALS AND METHODS: We subjected 88 rats to autologous external jugular vein grafting surgery randomly assigned to be treated with bortezomib or vehicle. After 24 or 72 hours, rats were humanely killed and vein grafts processed for real-time RT-PCR (24 and 72 hours), ELISA (24 hours), or neutrophil chemotaxis assay (24 hours). Subsequently, rats were humanely killed at 1 and 2 weeks after grafting with samples processed for morphometric analysis. RESULTS: Bortezomib significantly inhibited IH at 2 weeks compared with untreated controls (P < .05). Expression of mRNA for vascular cell adhesion molecule-1, intercellular adhesion molecule-1, cytokine-induced neutrophil chemoattractant 2beta, monocyte chemoattractant-1, interleukin (IL)-1, IL-6, and tumor necrosis factor-alpha markedly increased in injured vessels during the first day after surgery declining over the following 3 days. Bortezomib significantly attenuated gene expression and protein levels of most inflammatory mediators (P < .05), simultaneously inhibiting neutrophil chemotactic activity of vessel homogenates. CONCLUSIONS: Bortezomib inhibited neointimal formation at least partially by attenuating the inflammatory response in transplant-induced vasculopathy. It may become a novel vasoprotective agent in the clinical field.

[Regulation of dentin remineralization progress by non-collagenous protein analogues].

The use of various biomimetic methods to achieve remineralization of demineralized dentin and the formation of an organic matrix-inorganic mineral complex with a certain mechanical strength has been a research hotspot in recent years in the field of stomatology, and it also provides a new idea for the restoration of dentin defect. Dentin biomineralization is a process that simulates the mineralization of biological tissue in nature in which the remineralization of dentin collagen is induced and regulated by organic macromolecules. This review summarizes the process of remineralization of decalcified dentin regulated by non-collagenous protein analogues in vitro.

[Research progress in the application of implantoplasty in the treatment of peri-implantitis].

Peri-implantitis is a kind of serious complication after tooth implantation. The absorption of alveolar bone lead to the exposure of rough implant surface, which would result in poor long-term therapeutic effect. Implantoplasty promises a better long-term therapeutic effect than bone augmentation technique. This article will introduce implantoplasty from two aspects: therapeutic effect and its influencing factor, safety and effectiveness.

Thermoregulation responses of broiler chickens to humidity at different ambient temperatures. I. One week of age.

Three trials were conducted to investigate the effect of RH (35, 60, and 85%) on thermoregulation of 1-wk-old broiler chickens at different temperatures (35, 30, and 25 degrees C). The response to humidity in rectal temperature and plumage temperature at the back and breast within 24 h after exposure were recorded at 5 time points (1,4,8,16, and 24 h). Humidity affected the thermoregulation of 1-wk-old broiler chickens by redistributing heat within the body at high, low, and thermoneutral temperatures. The redistribution of heat resulted in decreased rectal temperature and increased peripheral temperature, which were, respectively, beneficial and unfavorable at high and low temperatures. These results suggested that feedback effects of surface temperature on core temperature also exist in poultry, as already observed in mammals, and could be induced not only by changed ambient temperature but also by the changes in humidity at high temperature. The disturbance of thermal equilibrium could not be established solely by changes in RT, but rather core and surface temperatures had to be considered. The daily rhythms in rectal and surface temperatures were affected by humidity.

Thermoregulation responses of broiler chickens to humidity at different ambient temperatures. II. Four weeks of age.

Two experiments were conducted to investigate the effect of RH (35, 60, and 85%) on thermoregulation of broiler chickens at high (35 degrees C) and mild (30 degrees C) temperatures at the age of 4 wk. The effects of humidity on rectal temperature (RT) and plumage temperature at back (PBAT) and skin temperature at breast (SBRT) were determined at 1, 4, 8, 16, and 24 h after exposure. The RT, PBAT, and SBRT were all significantly increased by high temperature (35 degrees C). Humidity had a significant influence on RT at 35 degrees C but not at 30 degrees C. The peripheral temperatures (PBAT and SBRT) were significantly affected by humidity but responded differently at high (35 degrees C) compared with mild temperature (30 degrees C). In conclusion, high humidity above 60% impaired the heat transmission from body core to the periphery at 35 degrees C but facilitated it at 30 degrees C in 4-wk-old broiler chickens. The effect of humidity on nonevaporative heat loss was depended on air temperature, as nonevaporative heat loss was suppressed by high humidity (>60% RH) at high temperature but enhanced at the mild temperature. The effect of humidity on the relationship between peripheral and core temperature depends on ambient temperature as well as on the age of the broiler chicken. The disturbance of thermal balance could not be determined only by changes in RT or peripheral temperature at a single time point but could be determined by mean body temperature within a certain time frame.

Design, synthesis, and monoamine transporter binding site affinities of methoxy derivatives of indatraline.

A series of methoxy-containing derivatives of indatraline 13a-f and 17 were synthesized, and their binding affinities for the dopamine, serotonin, and norepinephrine transporter binding sites were determined. Introduction of a methoxy group to indatraline affected its affinity and selectivity greatly. Except for the 4-methoxy derivative 13a,which had the same high affinity at the dopamine transporter binding site as indatraline, the other methoxy-containing analogues (13b-f and 17) exhibited lower affinity than indatraline for the three transporter binding sites. However, some of the analogues were more selective than indatraline, and the 6-methoxy derivative 13c displayed the highest affinity for both the serotonin and norepinephrine transporters. This compound retained reasonable affinity for the dopamine transporter and is a promising template for the development of a long-acting inhibitor of monoamine transporters. Such inhibitors have potential as medications for treatment, as a substitution medication, or for prevention of the abuse of methamphetamine-like stimulants.

Developmental pattern and distribution of nerve growth factor low-affinity receptor immunoreactivity in human spinal cord and dorsal root ganglia: comparison with synaptophysin, neurofilament and neuropeptide immunoreactivities.

Immunocytochemical expression of the low-affinity nerve growth factor receptor was studied in human fetal and adult tissues using the monoclonal antibody ME20.4. In dorsal root ganglia, a few immunoreactive neurons were first detected in nine-week-old fetuses and many more were found in the following weeks of gestation. However, none was present in adult ganglia. The ME20.4-positive cells were larger than neurons immunostained by substance P, calcitonin gene-related peptide or galanin antibodies. In the spinal cord, fibres immunostained by ME20.4 appeared in a characteristic pattern that differed from the spatial and temporal distributions of synaptophysin- and neurofilament-immunoreactive fibres. Those expressing the low-affinity nerve growth factor receptor were only detected in regions containing collaterals of primary sensory axons: (i) in the dorsal funiculus between seven and 18 weeks of gestation; (ii) in a ventrodorsal bundle reaching the ventral horn from weeks 12-14; (iii) in the medial region of the dorsal horn between weeks 12 and 20; (iv) in the superficial layers and lateral portion of the dorsal horn after the 14th week of gestation and also in adult spinal cord. During the fetal period, ME20.4 immunoreactivity was also found in motoneurons and peripheral nerve fibres in the skin, myotomes and gut. Sheaths of peripheral nerves and the adventitia of blood vessels were stained both in fetal and adult tissues. Thus, the low-affinity nerve growth factor receptor is: (i) strongly expressed in the developing human nervous system; (ii) transiently associated with a subset of large primary sensory neurons and with motoneurons; (iii) transiently and sequentially expressed by various groups of sensory afferents to the spinal cord; (iv) permanently expressed by fibres in the superficial layers of the dorsal horn, Clarke's column, nerve sheaths and the adventitia of blood vessels.

Rapid proliferation of calcitonin gene-related peptide-immunoreactive nerves during healing of rat tibial fracture suggests neural involvement in bone growth and remodelling.

The nervous system may be actively involved in bone repair and in remodelling of callous tissue in bone fractures, as well as in the regulation of nociceptive impulses from the site of the trauma. The aim of this study was to assess the distribution and nature of the periosteal innervation of normal control bone and during bone healing subsequent to fracture of rat tibiae at seven, 14 and 21 days after experimental fracture using immunocytochemistry and image analysis quantification of the neuronal marker protein gene product 9.5 and sensory neuropeptide calcitonin gene-related peptide. At seven days, periosteal protein gene product 9.5- and calcitonin gene-related peptide-immunoreactive fibres showed dense ramifications and terminal sprouting. In addition to periosteum, the nerve fibres were found in the middle of the callus interspersed with inflammatory cells and penetrating into secondary minor fractures. At days 14 and 21 many tortuous nerves were found in the periosteum but not in mid callus. Image analysis quantification revealed a uniform increased proliferation of nerves after seven days. At 21 days, the intercept countings showed in excess of a three-fold increase of calcitonin gene-related peptide-immunoreactive nerve fibres compared with the normal control group (P > or = 0.0001) and were almost as numerous as protein gene product 9.5-immunoreactive fibres (P < 0.005). It is postulated that calcitonin gene-related peptide-containing sensory innervation may have a potential importance in the fracture vascular control, angiogenesis and osteogenesis in addition to a protective role against excessive fracture movement. The results are consistent with the neural involvement in bone growth and remodelling.

Protecting the vasculature: an eye toward the future.

Although calcium antagonists were originally developed for use in the management of patients with angina pectoris, they are now used in the management of other cardiovascular disorders, including hypertension. More recently, the calcium antagonists have been under investigation for their potential protective role in atherosclerosis. Coupled with these new possibilities for therapeutic use are the development of new, long-acting, tissue-specific calcium antagonists. Amlodipine belongs to this group, and although it is a dihydropyridine-based calcium antagonist, its pharmacologic profile differs from that of other dihydropyridine-based calcium antagonists. Differences include: different pH optimum for receptor binding, different rates of association and dissociation, and differences in allosteric interaction with the diltiazem and verapamil binding sites. Amlodipine, when given orally to rabbits receiving a high-cholesterol diet, reduces atheroma formation. Evidence of its ability to protect the vasculature is provided by its ability to significantly increase (p less than 0.001) survival in stroke-prone hypertensive rats.