Long-term clinical and histological safety and efficacy of the CO2 laser for treatment of genitourinary syndrome of menopause: an original study.

OBJECTIVE: This study aimed to evaluate histological modifications of the vaginal mucosa after repeated microablative fractional CO2 laser treatments. As secondary objectives we evaluated the clinical effects associated with repeated microablative fractional CO2 laser treatments using validated questionnaires. METHODS: A prospective intervention study was performed in the Division of Gynecology and Obstetrics, Urogynecology Unit, IRCCS San Raffaele Scientific Institute with 15 postmenopausal women complaining of genitourinary syndrome of menopause symptoms. The cohort of patients was submitted to at least two previous laser treatment cycles in the past years. The Vaginal Health Index (VHI), visual analog scale (VAS), Female Sexual Function Index (FSFI), Urinary Distress Inventory-6 (UDI-6), International Consultation on Incontinence Questionnaire - Urinary Incontinence (ICIQ-UI) and 5-point Likert scale were used. Moreover, histological examinations were carried out on all samples. RESULTS: At 4 weeks after the last treatment, the VHI score and all FSFI items were significantly increased compared with baseline. We observed a statistically significant decrease in both frequency and severity for all urinary symptoms after the follow-up. We observed a statistically significant increase in the number of epithelial cell layers with a consequent increase in epithelial thickness, in the number of glycogen-filled cells and in the number of papillae after the laser treatment. No signs of fibrosis were observed as neovascularization was observed in each woman. CONCLUSIONS: This is the first study demonstrating the histological persistency of efficacy in repeated annually laser treatment cycles, with tissue changes always leading to regenerative results without any sign of fibrosis. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT04868812 (release date: 27 April 2021).

Morphological evidences following pegylated filler treatment in human skin.

In this study, microscopic, histochemical and ultrastructural observations in human skin are presented, 8 months after an injection of a novel PEGylated filler. Morphological features demonstrated an excellent integration of the filler with the connective tissue components and an effective interpenetration with the ground substance. The filler appears uniformly distributed inside the hypodermis. No segregation or encapsulation of cells and other structures was observed nor evidence of immunological adverse reaction. Furthermore, observed ultrastructural modifications of fibroblasts supports a stimulatory effect of molecular components production of the extracellular matrix, contributing to the cutaneous connective tissue renewal.

In vitro evaluation of collagen production on human fibroblasts treated with hyaluronic acid peg cross-linked with micromolecules of calcium hydroxyapatite in low concentration.

Neauvia Stimulate® is a biocompatible, injectable hyaluronic acid (HA) filler (26 mg/ml) PEG cross-linked with 1% of calcium hydroxyapatite (CaHA) for facial soft-tissue augmentation that provides volume to tissues, followed by a process of neocollagenesis for improving skin quality. The aim of the present study is to evaluate the possible modulation of collagen synthesis after treating human fibroblasts cultured in vitro with the product (Lot. 160517-26-1/2 PEG). The experimental model proposed, despite being an in vitro system, allows the derivation of useful information to predict the possible activity of the product in further in vivo application. Human fibroblasts (PEU cells) were treated with the product for 24 h at increasing concentrations of compared to control (untreated cells). The modulation of collagen synthesis was evaluated using a specific colorimetric kit (Sircol, Soluble Collagen Assay Kit). Increment of collagen production, 37.62% and 97.39% at concentrations of 1.25 mg/ml and 2.5 mg/ml of product, respectively, was considered to be statistically significant (*p values≤0.05 and **p values≤0.01) when compared with control (untreated cells). In conclusion, Hyaluronic Acid Hydrogel 26 mg/ml PEG cross-linked with calcium hydroxyapatite in low concentrations (1%) determines a statistical increment in neocollagenesis.

Clinical and histological changes in Hidradenitis suppurativa following 1064 nm nd:YAG intralesional laser treatment.

Hidradenitis Suppurativa (HS) is recently attracting much attention and awareness, often because it is misdiagnosed for years, restricting the therapeutic options. Moreover, this pathology arises in areas such as the inguinal region, that may cause embarrassment in young patients. Wrong diagnosis and delay in appropriate treatments lead to an exacerbation of the symptoms and a progression of the disease, which at the last stage can only be managed through extensive surgical excisions, ablation and vaporization of nodules with CO2 laser systems or aggressive chemotherapies such as anti-TNF-alpha like adalimumab (Humira®-AbbVie Inc. North Chicago, Illinois USA). In our study, we present an alternative low-invasive treatment that presents a successful outcome, supported by clinical and histological evaluation, limited however only for early stages of HS, highlighting the importance of raising awareness among physicians and patients by stressing the importance of an early diagnosis.

A new hyaluronic acid polymer in the augmentation and restoration of labia majora.

Aesthetic surgery of female external genitalia has gained increasing popularity over the past decade, with reduction of the labia minora (labiaplasty) being the procedure most commonly requested and performed. Female external genitalia lose elasticity and volume with age, but few studies describe the techniques for labia majora augmentation. Currently, very few studies have investigated the effectiveness and safety of labia majora augmentation with hyaluronic acid (HA) injection. This study aims to evaluate the effectiveness and safety of labia majora augmentation with hyaluronic acid filler injection. We retrospectively analyzed 37 patients affected by hypotrophy of the labia majora, treated with HA dermal filler 28mg/ml PEG crosslinked (Neauvia® Intense Rose, Matex Lab, Switzerland) between May 2015 and July 2016. Global evaluation of the aesthetics of the intimate area and clinical data were investigated with VAS (Visual Analogic Scale) ad hoc. Adverse events and complications were recorded. A total of 37 women affected by labia majora hypotrophy were treated with 28mg/ml HA dermal filler. A significant clinical improvement was observed in the score provided by both patients and doctor. Only mild adverse events and complications were recorded. HA hydrogel with a novel crosslinking agent is able to provide a considerable rejuvenation with a simple outpatient procedure and to bring a significant clinical improvement. HA-based filler infiltration treatment in labia majora is repeatable, has virtually no complications, and is reversible.

Are biological drugs safe in pregnancy?

The introduction of biological therapies has significantly improved the outcome of inflammatory rheumatic diseases. As most of these diseases affect women and men in childbearing age, some concerns have been voiced as to the safety of these drugs in relation to reproduction and pregnancy. Data from many hundreds of pregnancies in patients affected by inflammatory bowel disease and inflammatory arthritis have suggested that exposure to anti-TNF therapies at conception and/or during pregnancy is not associated with adverse pregnancy outcomes or any increase in congenital abnormalities. However, the exposure to anti-TNFα agents, particularly to monoclonal antibodies, in late pregnancy is associated with high drug levels in the newborn and their long-term effects on children remain unknown. Therefore, limiting the use of anti-TNFα to the first 30 weeks of pregnancy is recommended to reduce fetal exposure. Live-virus vaccines should be given only when levels of anti-TNFα drugs are undetectable in the serum of infants. Studies suggest that many of these drugs do enter breast milk in small amounts, but the extent to which the infant absorbs them is less clear. Limited reports have not suggested adverse pregnancy outcomes in women whose partners were exposed to anti-TNF therapies at the time of conception. Pregnancy data for rituximab, abatacept, anakinra, tocilizumab and belimumab are limited and their use in pregnancy cannot currently be recommended.

A 12-week treatment with fractional CO2 laser for vulvovaginal atrophy: a pilot study.

OBJECTIVE: This pilot study aimed to assess the efficacy and feasibility of fractional CO2 laser in the treatment of vulvovaginal atrophy (VVA) in postmenopausal women. METHODS: VVA symptoms were assessed before and after three applications of laser over 12 weeks in 50 women (age 59.6 ± 5.8 years) dissatisfied with previous local estrogen therapies. Subjective (visual analog scale) and objective (Vaginal Health Index Score, VHIS) measures were used during the study period to assess VVA. Quality of life was measured by using the SF-12. A subjective scale to evaluate the degree of pain related to the laser application and the degree of difficulty to perform the laser procedure was used. RESULTS: Fractional CO2 laser treatment was effective to improve VVA symptoms (vaginal dryness, vaginal burning, vaginal itching, dyspareunia, dysuria; p < 0.001) at 12-week follow-up, as well as the VHIS (13.1 ± 2.5 at baseline vs. 23.1 ± 1.9; p < 0.001). Both physical and mental scores of quality of life were significantly improved in comparison with baseline (p < 0.001). Satisfaction with the laser procedure was reported by 42 women (84%) and a minimal discomfort was experienced at the first laser application, mainly because of the insertion and the movements of the probe. Finally, the technique was very easy to perform in all women starting from the second application at week 4 and no adverse events were recorded during the study period. CONCLUSIONS: A 12-week treatment with the fractional CO2 laser was feasible and induced a significant improvement of VVA symptoms by ameliorating vaginal health in postmenopausal women. Further controlled studies should be performed to confirm the present data and to assess the long-term effects of the laser procedure on vaginal tissues.

Risk-based secondary prevention of obstetric antiphospholipid syndrome.

Treatment of pregnant women with antiphospholipid syndrome (APS) should be set apart from that from thrombotic APS patients. Patients with a history of pregnancy morbidity but no vascular thrombosis are usually treated with a prophylactic dose of heparin plus low-dose aspirin; whereas, those with previous vascular thrombosis alone or associated with previous pregnancy morbidity, are commonly treated with a therapeutic dose of heparin generally combined with low-dose aspirin. However, in about 20% of pregnant APS women these regimens fail. In this context, we conducted a case-control study on a large multicentre cohort of conventionally treated pregnancies to verify whether specific laboratory profiles and/or clinical characteristics are predictive of unsuccessful pregnancy outcome during conventional treatments. Multivariate analysis showed that pregnancy failure during conventional therapies was independently associated with a history of both thrombosis and pregnancy morbidity, the presence of systemic lupus erythematosus (SLE) or other systemic autoimmune diseases and triple antiphospholipid antibody positivity. With the aim to discover the most effective and safe treatments in high-risk pregnant APS women a large-scale multicentre study focusing on the effect of treatments on pregnancy outcome in women with APS and further risk factors for pregnancy failure has been designed.

Clinical value of anti-domain I-ß2Glycoprotein 1 antibodies in antiphospholipid antibody carriers. A single centre, prospective observational follow-up study.

BACKGROUND: There seems to be a clear correlation between antibodies against domain I (anti-DI) of ß2Glycoprotein I and severe clinical profiles in antiphospholipid syndrome (APS) patients. We investigated the clinical significance of anti-DI antibodies in a cohort of aPL carriers. METHODS: One hundred and five carriers persistently positive for IgG anti-ß2Glycoprotein 1 antibodies (a-ß2GPI) and/or IgG anticardiolipin (aCL) and/or lupus anticoagulants (LAC) were tested for the presence of anti-DI antibodies using the QUANTA Flash® Beta2GPI-Domain I chemiluminescence immunoassay. RESULTS: Anti-DI antibodies were detected in 44 aPL carriers (41.9%) and they were significantly associated to triple aPL positivity (LAC plus IgG a-ß2GPI plus IgG aCL antibodies). Isolated LAC and a-ß2GPI antibodies were significantly associated to anti-DI negative aPL carriers. During a 82.2 month mean follow-up, ten aPL carriers (9.5%) developed a first thrombotic event so becoming APS patients. Anti-DI antibodies, triple aPL positivity, thromboembolic risk factors and autoimmune disorders significantly prevailed in carriers becoming APS. Logistic regression analysis showed that anti-DI positivity was an independent risk factor for thrombosis. CONCLUSIONS: Anti-DI antibody positivity can be considered a new risk factor predictive of the first thrombotic event in aPL carriers, instead, negative anti-DI may be useful to identify low-risk aPL carriers.

Thrombocytopenia in high-risk patients with antiphospholipid syndrome.

Essentials The prevalence of thrombocytopenia in patients with antiphospholipid syndrome is not well defined. We studied triple positive patients with antiphospholipid syndrome and its catastrophic variant. Prevalence of thrombocytopenia was 6% and 100% in patients who developed the catastrophic form. In triple positive patients thrombocytopenia is low and platelets drop during the catastrophic form. SUMMARY: Background Thrombocytopenia is the most common non-criteria hematological feature in patients with antiphospholipid syndrome (APS). This condition is more common in patients with catastrophic APS (CAPS). Objectives To evaluate the prevalence of thrombocytopenia in a large series of high-risk patients with APS, and to assess the behavior of the platelet count during CAPS. Methods/Patients This was a cross-sectional study in which we analyzed the platelet counts of a homogeneous group of high-risk APS patients (triple-positive). Six of these patients developed a catastrophic phase of the disease, and the platelet count was recorded before the acute phase, during the acute phase, and at recovery. Results The mean platelet count in 119 high-risk triple-positive patients was 210 × 109 L-1 . With a cut-off value for thrombocytopenia of 100 × 109 L-1 , the prevalence of thrombocytopenia was 6% (seven patients). No difference between primary APS and secondary APS was found. In patients who suffered from CAPS, a significant decrease from the basal count (212 ± 51 × 109 L-1 ) to that at the time of diagnosis (60 ± 33 × 109 L-1 ) was observed. The platelet count became normal again at the time of complete remission (220 ± 57 × 109 L-1 ). A decrease in platelet count always preceded the full clinical picture. Conclusions This study shows that, in high-risk APS patients, the prevalence of thrombocytopenia is low. A decrease in platelet count was observed in all of the patients who developed the catastrophic form of the disease. A decrease in platelet count in high-risk APS patients should be considered a warning signal for disease progression to CAPS.

Models of epithelial histogenesis.

Epithelial tissues emerge from coordinated sequences of cell renewal, specialization and assembly. Like corresponding immature tissues, adult epithelial tissues are provided by stem cells which are responsible for tissue homeostasis. Advances in epithelial histogenesis has permitted to clarify several aspects related to stem cell identification and dynamics and to understand how stem cells interact with their environment, the so-called stem cell niche. The development and maintenance of epithelial tissues involves epithelial-mesenchymal signalling pathways and cell-matrix interactions which control target nuclear factors and genes. The tooth germ is a prototype for such inductive tissue interactions and provides a powerful experimental system for the study of genetic pathways during development. Clonogenic epithelial cells isolated from developing as well mature epithelial tissues has been used to engineer epithelial tissue-equivalents, e.g. epidermal constructs, that are used in clinical practise and biomedical research. Information on molecular mechanisms which regulate epithelial histogenesis, including the role of specific growth/differentiation factors and cognate receptors, is essential to improve epithelial tissue engineering.

[Primary antiphospholipid syndrome and hyperhomocysteinemia: a study of a group of 29 patients]. / Sindrome da anticorpi antifosfolipidi primaria e iperomocisteinemia: studio di un gruppo di 29 pazienti.

OBJECTIVE: In order to investigate the potential role of hyperhomocysteinemia as an additional risk factor for thrombotic events, we studied its prevalence in patients with primary antiphospholipid syndrome (APS) and evaluated its association with different clinical features. METHODS: We enrolled 29 patients without any current evidence of underlying connective tissue disorder and fulfilling the Sapporo preliminary classification criteria for APS. RESULTS: Ten (34,4%) patients showed mild hyperhomocysteinemia (18,34 micromol/L +/- 2,04 DS). Nine had history of cerebrovascular disease, isolated (3 cases) or more often (6 cases) in association with other APS features. All patients, but one, showed multiple ischemic cerebral lesions. Seven of the 10 patients with hyperhomocysteinemia had multiple antiphospholipid antibody positivity and presented more frequently (6 cases) multi-site vascular involvement. CONCLUSIONS: The frequency of hyperhomocysteinemia in patients with primary APS is not negligible and appears to be associated with cerebral microangiopathic disease, multiple antiphospholipid antibody positivity and the simultaneous involvement of different vascular districts. For this reason and because hyperhomocysteinemia can be easily corrected with safe and relatively inexpensive therapeutic interventions, we advocate the measurement of homocysteinemia in every patient affected by APS and possibly in subjects with positive antiphospholipid antibody without a history of thrombosis.

[Isolated congenital heart block in undifferentiated connective tissue disease and in primary Sjögren's syndrome: a clinical study of 81 pregnancies in 41 patients]. / Il blocco cardiaco congenito nella connettivite indifferenziata e nella sindrome di Sjögren primitiva. Studio di 81 gravidanze in 41 pazienti.

OBJECTIVE: To study the incidence and the features of congenital heart block (CHB) in patients with undifferentiated connective tissue disease (UCTD) and primary Sjögren's syndrome (pSS). METHODS: We studied 81 pregnancies of 41 women attending the Outpatients' Clinic of the Rheumatology Unit of University Hospital of Padova from July 1989 to March 2004. Twenty five of these (61%) were affected with UCTD and 16 (39%) with pSS. Serologic inclusion criteria was anti-Ro/La positivity, assessed by counterimmunoelectrophoresis and ELISA. RESULTS: CHB was found in 2 out of the 46 (4.3%) pregnancies followed by our Staff and in 2 out of the 35 (5.7%) included in the retrospective part of the study. In 3 cases CHB was a 3rd degree block, causing pregnancy termination in 2. The only 2nd degree block was identified in one patient at the 22nd week of gestation and treated with dexamethasone and plasma-exchange. All of the women were positive to 52 kd and 60 kd Ro autoantibodies. CHB mothers had higher titer antibodies to 52 kd Ro protein than did the mothers with healthy infants (P = 0.026). Electrocardiographic abnormalities at birth were found in 3 out of 29 asymptomatic infants. One presented sinus bradycardia, the second abnormalities of ventricular repolarization, both regressed spontaneously, while the third ventricular extrasystoles which continue even now at 5 months. CONCLUSIONS: These results showed that in UCTD and pSS there is a higher incidence of CHB than that reported in Systemic Lupus Erythematosus. Electrocardiographic screening in all infants born to mothers with anti-Ro/La antibodies would seem an important measure to identify those with irreversible heart conduction abnormalities.

Early effects of AZT on mitochondrial functions in the absence of mitochondrial DNA depletion in rat myotubes.

Zidovudine (AZT) is a potent inhibitor of human immunodeficiency virus (HIV) replication. In humans, as well as in animal models, long-term treatment with AZT induces a severe myopathy characterised by structural and functional alterations of mitochondria associated with depletion of mitochondrial DNA (mtDNA). In the present work, we compared the effects induced by AZT on mitochondria upon short- or long-term treatments of cultured rat myotubes. Morphological alterations were investigated by electron microscopy, and mtDNA depletion and deletions were analysed by Southern blot. Mitochondrial membrane potential was determined after JC-1 staining by laser-scanning confocal microscopy in whole cells, and by flow cytometry in isolated muscle mitochondria. We found that the early effects of AZT on mitochondrial functions were a marked, yet reversible reduction in mitochondrial membrane potential, in the absence of any effect on mtDNA. The long-term treatment, in addition to mitochondrial membrane potential alterations, induced morphological changes in mitochondria, and a remarkable reduction in the amount of mtDNA, without any significant evidence of mtDNA deletions. In both treatments, a block of the spontaneous contraction of myotubes was observed. To study in more detail the early effects induced by AZT, the ability of the drug to interact with cardiolipin, an important component of internal mitochondrial membrane, was investigated by atomic force microscopy (AFM) in an artificial membrane model system. The results suggest that the primary effects of AZT may be related to a physical interference with the membrane structure leading to a consequent modification of its physical characteristics.

Immunohistochemical localization of lipoperoxidation products in normal human placenta.

4-Hydroxynonenal (4-HNE) is a major propagation product of lipid peroxidation that is supposed to be responsible for some of the effects associated with oxidative stress in tissues. We have investigated the possible occurrence and distribution of 4-HNE-immunoreactivity in human normal placenta using immunocytochemistry. Specific immunostaining was observed in cytotrophoblast cells, syncytiotrophoblast, some cells of the villous mesenchyme and some endothelial cells of first trimester and term placentae. The detection of 4-HNE-immunoreactivity in placenta raises the question whether lipoperoxidation products are produced locally in placental cells or represent exogenous products that derive from maternal blood flow. Since trophoblastic cells and villous macrophages are provided by a scavenger receptor, it is conceivable that these cells may play a protective role with regard to the diffusion of lipoperoxidation products from the mother to the embryo. However, since a significant degree of lipid oxidative modification does not take place in plasma, it is presumed that 4-HNE is a local product of placental metabolism. In line with this hypothesis, it is proposed that maternal low density lipoproteins, which are the major source of cholesterol for placental steroid synthesis, might be oxidized by villous cells during their traversal through the villous wall.

Detection and quantitation in rat tissues of the superparamagnetic magnetic resonance contrast agent dextran magnetite as demonstrated by electron spin resonance spectroscopy.

RATIONALE AND OBJECTIVES: The compound studies in this article is a superparamagnetic macromolecular complex of magnetite cores coated with hydrophilic dextran, which is under active investigation as a contrast agent for magnetic resonance imaging (MRI) in liver and spleen. The biodistribution of paramagnetic compounds is problematic and is usually studied by histochemical reactions or by radiolabeling the compound under study. The purpose of this article is to show how electron spin resonance (ESR) spectroscopy detects dextran magnetite (DM) particles in tissues. METHODS: DM injected intravenously in the experimental animal was detected in some reticulo-endothelial organs by ESR. The spectroscopic study was validated using electron microscopy and electron-probe microanalysis. RESULTS: DM exhibits an ESR spectrum; ESR delineated the distribution of DM distribution in liver, spleen, bone marrow, and blood as a function of time. The blood clearance was biphasic, dependent on the size of particles. CONCLUSIONS: ESR spectroscopy is a highly sensitive and reproducible method of studying DM distribution.

Differential distribution of elastic tissue in human natural skin and tissue-engineered skin.

Tissue-engineered skins (TES), manufactured by epidermal and dermal equivalents, are now being used in biological, pharmacotoxicological and clinical applications. It is thus interesting to know to what extent artificial organs are similar to natural counterparts. Elastic fibres are important constituents of the extracellular matrix of natural skin (NS). The aim of our study was to investigate the possible occurrence and distribution of elastic tissue in a model of human TES using different histochemical techniques, including classical Orcein and Fuchsin-Resorcin methods and immunohistochemistry, at both light and electron microscopical levels. Immunoperoxidase and high resolution immunogold methods were used. In NS, classical staining techniques and elastin-immunohistochemistry revealed a well-organized network of elastic fibres. High resolution immunocytochemistry revealed an intense labelling in the amorphous component of elastic fibres. Fibres of different diameters were immunostained. In TES, no stained elastic fibres were observed using classical staining techniques, and the interpretation of immunoperoxidase observations was not clear-cut. In contrast, immunogold staining at the electron microscopical level provided specific labelling of elastin-like immunoreactive material in the dermal equivalent. However, ultrastructural immunocytochemistry revealed that elastic tissue organization in TES was poor compared to that in NS. This study demonstrates that elastic fibres are a component of the extracellular matrix in this model of TES and suggests that fibroblasts of the dermal equivalent are engaged in matrix secretion. Nevertheless, the level of extracellular matrix organization in TES is low compared to NS. Moreover, this study also suggests that different models of bilayered TES may differ with respect to extracellular matrix organization. These aspects should be considered when TES is used in biological and pharmacotoxicological studies. A better understanding of the factors influencing extracellular matrix formation in TES is necessary to achieve further development of skin generation in vitro.

Prevalence and characteristics of anti-single-stranded DNA antibodies in localized scleroderma. Comparison with systemic lupus erythematosus.

Prevalence, levels, and immunoglobulin classes of anti-single-stranded DNA antibodies were determined by an enzyme-linked immunosorbent assay in 52 patients with localized scleroderma (33 with morphea, four with generalized morphea, and 15 with linear scleroderma), in 60 healthy controls, and, for comparison, in 31 patients with systemic lupus erythematosus. Localized scleroderma revealed a significant prevalence of anti-single-stranded DNA antibodies, mainly characterized by high levels and IgM and IgA isotypes. Comparison of antibody characteristics in different clinical forms of localized scleroderma showed some significant differences (levels and immunoglobulin isotypes). Comparison with systemic lupus erythematosus showed that frequency, high levels, and IgG isotype of anti-single-stranded DNA antibodies significantly prevailed in systemic lupus erythematosus, while the IgM isotype significantly prevailed in localized scleroderma. However, generalized morphea and linear scleroderma did not significantly differ from systemic lupus erythematosus as regards antibody frequency and prevalence of high antibody levels.

Immunocytochemical evidence for the presence of somatostatin-like immunoreactive nerves in human dental pulp.

Specific antiserum to somatostatin was used for the immunocytochemical detection of this neuropeptide in human dental pulp. Immunoreactive axon varicosities were observed in the radicular as well as coronal pulp. Fibers displaying somatostatin-like immunoreactivity were detectable within radicular nerve trunks and were found to be associated mainly with blood vessels. Nevertheless, positive fibers with no apparent relation to blood vessels were also observed. No pulp cell was found to be immunoreactive. Previous physiological studies demonstrated that somatostatin may function as a regulatory peptide in feline dental pulp via a pre-synaptic inhibition of substance P release from sensory nerve terminals. It is tempting to speculate that such a mechanism may also be effective in human teeth and may be of value in the regulation of pulpal blood flow and in situations when sensory nerve fibers are activated, e.g., during pulpal inflammation.