Documents

Viability of the indication and use of cyclamen extract in Clinical practice

PISKUNOV, G.
Head of the ORL Department,
Russian Medical Academy of Postgraduate Education. Russia

New Treatment Approaches to Rhinosinusitis: Less is more.
Crete. Greece. 15-19 June 2008
Keywords New Treatment approaches to Rhinosinusitis - PDF

ABSTRACT

A study carried out on rabbits using cyclamen extract to measure histological, histochemical, functional and morphological changes has concluded that the preparation is associated with a quick-acting, marked stimulation of mucus synthesis and release from the mucous glands of the nasal cavity and maxillary sinus. Both this stimulation and the structural changes of the mucosa are reversible.

Another study performed on humans with Acute Bacterial Rhinosinusitis, comparing treatment with cyclamen extract and conventional therapy, has shown that mucociliary transport (MCT) along the nasal cavity mucous membrane increases significantly in patients treated with cyclamen. Similar results are obtained in both treatment groups as regards clinical evolution and results of the X-rays and CT scans.

The development of catarrhal inflammation is a natural pathophysiological reaction by the mucous membrane to invasion by a harmful agent. Catarrhal inflammation of the mucous membrane develops as a serous inflammation with hypersecretion from the glandular and respiratory epithelium; the inflammation triggers the reaction by the blood vessels comprising the microcirculation of the mucous membrane.

On the basis of these facts, Professor Piskunov talked about the possibility of interfering with secretion by the mucous glands. He presented the results of a study that assessed the secretory function of the mucous glands in rabbit paranasal sinuses. Three hours after administration of pilocarpine, almost all of the secretions had exited the alveolar and alveolar-tubular gland cells. Administration of atropine delays release of the secretion for 3 hours (the gland cells are in the secretion accumulation stage). A secretory cycle of the alveolar gland cells lasts for 15-16 hours and almost 24 hours in the case of the alveolar-tubular gland cells. As the speaker remarked, this shows the asynchronicity of the mucous gland cells’ function.

The asynchronicity of the mucous gland cells’ function provides the basis for the presence of an appropriate quantity of mucus on the mucosal surface. This asynchronicity assures normal functioning of the mucociliary transport system.

The hypersecretion is a pathophysiological phenomenon that helps the body eliminate the pathogen from the mucosa and restore the mucosa’s normal structure and function. The secretion is a complex intracellular process in which the gland cells use substances from the blood to synthesize specific components, accumulate them and secrete them to the surface, with the specific goal of fighting infection. This process can be structured into three phases or stages: arrival of the originating substances; production and accumulation of the secretion; and release of the secretion.

EFFECTS OF SINUFORTE®

The effects of the administration of Sinuforte® on the function of the glands in the nasal cavity and maxillary sinus mucosa have been studied. Piskunov et al.’s study included the performance of quantitative histological and histochemical examinations to determine the mucous glands’ response to the intranasal administration of cyclamen extract. The morphological and functional changes that take place in the epithelium and stromal structures of the nasal cavity and the maxillary sinus mucosa after administration of Sinuforte® have also been measured.

The study was carried out on 8 Florida white rabbits weighing 1.5-2 kg. Sinuforte® was administered at the concentration normally used in clinical practice (0,13 ml in each nostril). The animals were killed by air embolism 30 minutes, 1 hour and 3 hours after administration of the drug. The nasal cavity was opened along the nasal dorsum and the maxillary sinus mucosa was carefully removed. The histological preparations were studied in blind conditions and coded. This coding was maintained until the end of the study. Histological and histochemical examinations were performed on the materials obtained, using digital microscopy and computerised analysis of the images obtained.

This study has sought to determine the zonal specificities in the mucous glands’ location and structure, changes in the glands’ secretory activity during the experiment, and the effect on the blood and lymph vessels.

Regarding zonal specificities in the mucous glands’ location and structure, all of the areas studied in the nasal cavity and maxillary sinus mucosa show well-defined glandular structures, represented by terminal portions of alveolar and alveolar-tubular mucosa that have a typical microscopic structure.

As regards the changes in the glands’ secretory activity, a statistically significant effect by the product on secretion and stimulation is already observed just 30 minutes after administration on the lateral wall of the nasal cavity in certain areas of the nasal septum and maxillary sinus. The secretory activity was synchronised and stimulated. One hour after administration of the cyclamen extract, all parts of the mucosa show qualitative and quantitative changes that indicate recovery of the glands (attaining a situation similar to baseline). The secretory cells’ cytoplasm in the glands’ terminal portions takes on a granular structure, with a more marked increase in the number of eosinophils (something that is observed in all parts of the mucosa studied: the lateral walls, septum and maxillary sinus).

The histochemical data also indicate a return to baseline status by the secretory cells. The initial accumulation of PAS-positive granules was observed in the septal region and maxillary sinus. Three hours after administration of Sinuforte®, the morphological appearance of the mucous glands in the nasal cavity indicated a complete recovery to the baseline situation. Use of this product does not cause any damage to the epithelial lining nor does it generate inflammatory reactions; all of the changes documented are within a range of physiological variation of glandular secretory activity.

The treatment’s effects on blood and lymph vessels were also assessed. The superficial and deep blood vessels of the nasal septum, lateral wall and maxillary sinus mucosa were seen to dilate just 30 minutes after use of Sinuforte® (there are also dilated arteries in the surface layer of the nasal cavity mucosa).

In summary, the main findings observed in this trial are the following: the existence of zonal specificities for mucous gland location and structure in the nasal cavity and maxillary sinus; there is a higher concentration and diversity of glandular elements in the mucosa of the lateral nasal wall and a lower concentration in the septal mucosa. Intranasal administration of Sinuforte® is associated with characteristic morphological signs that show a marked stimulation of the synthesis and release of the secretion in the mucous glands of the nasal cavity and maxillary sinus. The stimulation-secretion effect is seen within the first 30 minutes after administration of one dose of Sinuforte®; 1-3 hours after administration of the product, the structure of the mucous glands and the content of the mucous components return to their baseline condition. The vasodilatory effect caused by the cyclamen extract suggests stimulation of the blood and lymph flow in the nasal cavity and maxillary sinus mucosa. “Sinuforte® is capable of using physiological means to cure the rhinosinusitis,” concluded Professor Piskunov.

SINUFORTE® IN ACUTE BACTERIAL RHINOSINUSITIS

Another study presented by Professor Piskunov has sought to determine the clinical efficacy of cyclamen extract in patients with acute bacterial rhinosinusitis, that is, acute inflammation of the nasal mucous membrane and paranasal sinuses caused by bacterial microflora. Normally, a range of resources is used to treat this condition in Russia: vasoconstrictive drops, antibiotics, antihistamines, symptomatic treatments, sinus puncture or drainage, YAMIK-catheter.

Among these resources, direct puncture of the maxillary sinuses has been the standard treatment for many years in Russia for acute bacterial rhinosinusitis; however, as Dr. Piskunov highlighted, “this procedure can cause serious complications: orbit puncture, subcutaneous puncture, invasion of the pterigopalatine fossa, epistaxis, local pain caused by the puncture itself,....” For their part, vasoconstrictors improve nasal breathing and reduce rhinorrhea but also reduce microcirculatory blood flow. As regards the use of antibiotics, there is the risk of developing dysbacteriosis in early rhinosinusitis, the inflammation is most often caused by viral infection, and antibiotics therapy is not effective; in addition, there are many patients who are allergic to these drugs, which are contraindicated in such cases.

In this context, comparing the effect of an alternative resource for the treatment of rhinosinusitis with that of traditional medicines was deemed advisable. This was also the case for evaluating the influence of Sinuforte® on nasal mucous membrane function. This product has been used with a view to accelerating the course of inflammation in rhinosinusitis patients, increasing secretory activity in the mucous membrane glands and microcirculatory blood flow.

The study has been carried out on a total of 62 outpatients diagnosed with acute bacterial rhinosinusitis. Patients with severe rhinosinusitis were excluded from the study. A total of 30 patients were included in the control group, while 32 were allocated to the Sinuforte® group. The patients in both groups had similar baseline features (most of them reported bilateral maxillary rhinosinusitis). Subjects with confirmed acute bacterial rhinosinusitis who signed an informed consent were included; patients under 14 years of age, with a history of allergy, with any form of bronchial asthma, pregnant or breastfeeding women, patients with high blood pressure, closed angle glaucoma, chronic polypous rhinosinusitis, odontogenic rhinosinusitis or suspected orbital or intracranial complications of rhinosinusitis were excluded.

Monotherapy Sinuforte for 7-9 days at one irrigation per day

The study was intended to detect the release of mucus into the middle and/or inferior nasal meatus during the videoendoscopy and, to achieve this purpose, the secretion from the middle nasal meatus was sampled under endoscopic control and a bacteriological study was performed. A frontal X-ray of the paranasal sinuses was performed and the MCT of the nasal mucous membrane and the severity of the disease (on the basis of the symptoms) were evaluated.

Group I (n=32) received Sinuforte® as single-agent therapy for 7-9 days with a single daily administration, accompanied by irrigation of the nasal cavity with sterile isotonic saline solution (2-3 times a day). Group II (n=30) received amoxicillin-clavulanic acid or flemoxin, rinofluimicil, an antihistamine preparation and the nasal cavity was also irrigated with sterile isotonic saline solution (2-3 times a day). Three visits were scheduled, apart from the baseline visit: at visit 1, the effect of irrigation with Sinuforte® on the nasal mucous membrane was assessed 30 minutes after administration; visit 2 took place on treatment day 4-5; lastly, visit 3 took place after 7-9 days of treatment.

Dynamics of clinical symptoms in main group (with Sinuforte)

Results of endoscopic nosasoscopy in main group (with Sinuforte)

The spectrum of microorganisms identified is similar in both groups (S. pneumoniae, S. epidermidis, A. viridans and acinetobacteria).

The clinical symptoms and the results of the nasal endoscopy are also similar in both groups.

The analysis of the MCT of the mucous membrane of the inferior nasal turbinate shows some differences between the control group and the group treated with Sinuforte®.

Although no differences are documented in visits 0 and 3, there are statistically significant differences between the two groups in visit 2 (with a higher MCT in the control group).

MCT of mucous membrane of the inferior nasal concha in maing group (with Sinuforte)

The X-ray and the CT scan show that treatment with Sinuforte® is associated with significant benefits as it is confirmed that the sinuses show improved ventilation after treatment.

Before and after the treatment with Sinuforte® (radiogram), sinuses are better pneumatized

As Professor Piskunov summarised, “this study has confirmed that Sinuforte® stimulates glandular secretion in the nasal cavity and paranasal sinus mucosa.” The cyclamen extract is associated with a statistically significant physiological increase (p<0.05 at visit 2) in mucociliary transport by the nasal cavity mucous membrane. Sinuforte® also restores the mucous membrane. The clinical efficacy of the single-agent therapy with Sinuforte® is comparable to the effect achieved with traditional therapy in the treatment of acute bacterial rhinosinusitis. Therefore, the speaker concluded, Sinuforte® can be used for the treatment of acute bacterial rhinosinusitis as an alternative to traditional treatment resources and is associated with a good clinical efficacy.


New Treatment Approaches in Rhinosinusitis - Index

Is it possible to cure all forms of Acute Rhinosinusitis in 4 weeks? Evidence from the Prosinus study - Next Article

Hartington Pharma owns Nasodren® for sinusitis treatment