Polymorphonuclear neutrophils in periodontitis and their possible modulation as a therapeutic approach

The main focus of this review is polymorphonuclear neutrophilic granulocytes. Polymorphonuclear neutrophils play a pivotal role in normal host resistance to subgingival dental‐plaque biofilm. Both hyper‐ and hypo‐responsiveness of the immune system toward the microbial challenge in periodontitis have been described. We review polymorphonuclear neutrophil physiology with emphasis on the role of neutrophil functions and dysfunctions in periodontitis. Text boxes are given at the end of each subsection, which present the current knowledge on neutrophil‐modulating agents as a potential therapeutic approach in periodontitis.     

Cellulose-Based Hydrogels as Sustained Drug-Delivery Systems

Hydrogels, three-dimensional (3D) polymer networks, present unique properties, like biocompatibility, biodegradability, tunable mechanical properties, sensitivity to various stimuli, the capacity to encapsulate different therapeutic agents, and the ability of controlled release of the drugs. All these characteristics make hydrogels important candidates for diverse biomedical applications, one of them being drug delivery. The recent achievements of hydrogels as safe transport systems, with desired therapeutic effects and with minimum side effects, brought outstanding improvements in this area. Moreover, results from the utilization of hydrogels as target therapy strategies obtained in clinical trials are very encouraging for future applications. In this regard, the review summarizes the general concepts related to the types of hydrogel delivery systems, their properties, the main release mechanisms, and the administration pathways at different levels (oral, dermal, ocular, nasal, gastrointestinal tract, vaginal, and cancer therapy). After a general presentation, the review is focused on recent advances in the design, preparation and applications of innovative cellulose-based hydrogels in controlled drug delivery.     

Hyper-reactive PMNs in FcgammaRIIa 131 H/H genotype periodontitis patients

BACKGROUND: Receptors for the Fc part of IgG (FcgammaRIIa) on polymorphonuclear leukocytes (PMN) mediate phagocytosis and cell activation. Previous results show that one of the genetic variants of the FcgammaRIIa, the 131 H/H, is associated with more periodontal breakdown than the R/R. This may be due to hyper-reactivity of the H/H-PMNs upon interaction with bacteria. AIM: To study whether the FcgammaRIIa genotype modifies the PMN reactivity in periodontitis patients. MATERIAL AND METHODS: A cohort of 98 periodontitis patients was genotyped. From these, 10 H/H and 10 R/R consented to participate. PMNs were incubated with immune serum-opsonized Actinobacillus actinomycetemcomitans (A.a.). Phagocytosis, degranulation (CD63 and CD66b expression), respiratory burst and elastase release were assessed. Results: Patients of the H/H genotype showed more bone loss than those with the H/R or R/R genotype (p=0.038). H/H-PMNs phagocytosed more opsonized A.a. than did R/R-PMNs (p=0.019). The H/H-PMNs also expressed more CD63 and CD66b than did the R/R-PMNs (p=0.004 and 0.002, respectively) and released more elastase (p=0.001). CONCLUSIONS: The genotyping results confirm previous reports that more periodontal destruction occurs in the H/H genotype than in the H/R or R/R genotype. The functional studies indicate a hyper-reactivity of the H/H-PMN in response to bacteria, which may be one of several pathways leading to more periodontal breakdown.     

Dermal Adipose Tissue Secretes HGF to Promote Human Hair Growth and Pigmentation

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Clues that mitochondria are involved in the hair cycle clock: MPZL3 regulates entry into and progression of murine hair follicle cycling

The molecular nature of the hair cycle clock (HCC), the intrinsic oscillator system that drives hair follicle (HF) cycling, remains incompletely understood; therefore, all relevant key players need to be identified. Here, we present evidence that implicates myelin protein zero-like 3 (MPZL3), a multifunctional nuclear-encoded mitochondrial protein known to be involved in epidermal differentiation, in HCC regulation. By analysing global Mpzl3 knockout (−/−) mice, we show that in the absence of functional MPZL3, mice commence HF cycling with retarded first catagen-telogen transition after normal postnatal HF morphogenesis. However, Mpzl3 −/− mice subsequently display strikingly accelerated HF cycling, i.e. a precocious telogen-to-anagen transition during the second hair cycle, compared to controls, suggesting that MPZL3 inhibits anagen entry. We also show that intrafollicular MPZL3 protein expression fluctuates in a hair cycle-dependent manner. In telogen HFs, MPZL3 is localized to the secondary hair germ, an epicentre of hair cycle regulation, where it partially co-localizes with P-cadherin. In early anagen HF, MPZL3 is localized immediately distal to the proximal hair matrix. These findings introduce the novel concept that mitochondria are more actively involved in hair cycle control than previously recognized and that MPZL3 plays a central role in the HCC.     

Transient elevation of serum bile acids during acute pancreatitis

Summary An increase of serum bile acids was detected in patients with biliary acute pancreatitis who could be investigated during the first 24 hours after the onset of the acute phenomena. Serum bile acids levels, as well as α-amylase activity, however rapidly decreased and were found within normal limits after 48–72 h, while the increased serum γ-glutamyltransferase activity persisted for at least 7 days. Changes affecting serum bile acids in patients with acute pancreatitis unassociated to biliary disease or in patients with acute biliary disease unaccompanied by a pancreatic reaction were less important. Mechanisms leading to these changes and their possible pathogenic relevance are briefly discussed.     

Impaired polymorphonuclear neutrophils in the oral cavity of edentulous individuals

Oral health is characterized by functional oral polymorphonuclear neutrophils (oPMNs). Edentulism might be associated with a loss of oPMNs because these cells enter the oral cavity primarily through the gingival crevices. The main aim of this study was to investigate the numbers of oPMNs in rinse samples obtained from edentulous (n = 21) and dentate (n = 20) subjects. A second study aim was to investigate possible differences between oPMNs and peripheral blood polymorphonuclear neutrophils (cPMNs). Apoptosis/necrosis and cell‐activation markers (CD11b, CD63 and CD66b) were analyzed using flow cytometry. Reactive oxygen species (ROS) production was determined either without stimulation (constitutive) or in response to 10 μM phorbol myristate acetate or Fusobacterium nucleatum. The edentulous subjects presented with lower oPMN counts and higher percentages of apoptotic/necrotic oPMNs compared with dentate subjects. Furthermore, oPMNs from edentulous donors expressed low levels of all three activation markers and low constitutive ROS. In contrast, oPMNs from dentate subjects expressed high levels of all three activation markers and a higher level of constitutive ROS than cPMNs. When challenged, oPMNs from edentulous subjects showed no upregulation in ROS production, whereas oPMNs from dentate subjects retained their ability to respond to stimulation. The functional characteristics of cPMNs were comparable between edentulous and dentate subjects. This study demonstrates that despite having functional cPMNs, edentulous subjects have low oPMN numbers that are functionally impaired.     

Periodontitis is associated with platelet activation

There is an epidemiological association between periodontitis and cardiovascular disease (CVD). In periodontitis, low grade systemic inflammation and bacteremia occur regularly. Such events may contribute to platelet activation and subsequent pro-coagulant state. This study aimed to investigate platelet activation in periodontitis patients. The study is composed of two parts. In the first part, plasma levels of soluble(s) P-selectin and sCD40 ligand were measured as general markers of platelet activation in periodontitis patients (n=85) and in healthy controls (n=35). In the second part, surface-exposed P-selectin and the ligand-binding conformation of the glycoprotein IIb-IIIa complex (binding of PAC-1 antibody) were determined on individual platelets in whole blood of periodontitis patients (n=18) and controls (n=16). Patients had significantly elevated plasma levels of sP-selectin (P<0.001) and increased binding of PAC-1 on isolated platelets (P=0.033). Platelet activation was more pronounced in the patients with more severe periodontal disease, showing a severity-dependence. The levels of sCD40 ligand and of platelet-bound P-selectin were not increased. Periodontitis is associated with increased platelet activation. Since platelet activation contributes to a pro-coagulant state and constitutes a risk for atherothrombosis, platelet activation in periodontitis may partly explain the epidemiological association between periodontitis and CVD.     

Eccrine sweat glands associate with the human hair follicle within a defined compartment of dermal white adipose tissue

It has always been assumed that sweat glands are distributed throughout the skin unconnected with hair follicles (hair “roots”) and their associated sebaceous (or “grease”) glands, which, together with other specialised glands and the muscles that make hairs stand up, are known as pilosebaceous units. Sweat glands and pilosebaceous units, in other words, have always been considered separate structures, with sweat glands opening on to the skin surface between hairs rather than alongside them. Sweat glands on the palms of the hands and the soles of the feet develop differently and were not considered in this study. Using a number of techniques, including looking down the microscope at sections of hair follicles taken from the scalp during hair transplants, and at manual and computer‐assisted 3D reconstructions of sections of scalp skin, this study from Spain and Manchester, UK, suggests that in hair‐bearing areas the deepest part of the sweat gland, a coiled structure, is in fact located very close to the deepest part of the pilosebaceous unit, sitting right by the sheath of the hair follicle, below the sebaceous gland and the point where the hair muscle attaches. Moreover, these structures sit together within cone‐shaped projections of fat that reach upwards into the lowest layer of the skin, the thick reticular dermis, from the fat underneath. The authors speculate that sweat glands, pilosebaceous units and this particular fatty tissue (collectively the “adnexal skin unit”) may interact in certain skin diseases, during wound healing and with drug treatments.